RESUMO
BACKGROUND: Optimal consolidation for young patilents with relapsed/refractory (R/R) follicular lymphoma (FL) remains uncertain in the rituximab era, with an unclear benefit of autologous stem cell transplantation (ASCT). The multicenter, randomized, phase III FLAZ12 (NCT01827605) trial compared anti-CD20 radioimmunotherapy (RIT) with ASCT as consolidation after chemoimmunotherapy, both followed by rituximab maintenance. PATIENTS AND METHODS: Patients (age 18-65 years) with R/R FL and without significant comorbidities were enrolled and treated with three courses of conventional, investigator-chosen chemoimmunotherapies. Those experiencing at least a partial response were randomized 1 : 1 to ASCT or RIT before CD34+ collection, and all received postconsolidation rituximab maintenance. Progression-free survival (PFS) was the primary endpoint. The target sample size was 210 (105/group). RESULTS: Between August 2012 and September 2019, of 164 screened patients, 159 were enrolled [median age 57 (interquartile range 49-62) years, 55% male, 57% stage IV, 20% bulky disease]. The study was closed prematurely because of low accrual. Data were analyzed on 8 June 2023, on an intention-to-treat basis, with a 77-month median follow-up from enrollment. Of the 141 patients (89%), 70 were randomized to ASCT and 71 to RIT. The estimated 3-year PFS in both groups was 62% (hazard ratio 1.11, 95% confidence interval 0.69-1.80, P = 0.6662). The 3-year overall survival also was similar between the two groups. Rates of grade ≥3 hematological toxicity were 94% with ASCT versus 46% with RIT (P < 0.001), and grade ≥3 neutropenia occurred in 94% versus 41%, respectively (P < 0.001). Second cancers occurred in nine patients after ASCT and three after radioimmunotherapy (P = 0.189). CONCLUSIONS: Even if prematurely discontinued, our study did not demonstrate the superiority of ASCT versus RIT. ASCT was more toxic and demanding for patients and health services. Both strategies yielded similar, favorable long-term outcomes, suggesting that consolidation programs milder than ASCT require further investigation in R/R FL.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Folicular , Humanos , Masculino , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Adulto , Idoso , Feminino , Linfoma Folicular/radioterapia , Radioimunoterapia , Rituximab , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Transplante Autólogo , Transplante de Células-TroncoRESUMO
Background: The aim of this study was to evaluate patient preference and satisfaction for the subcutaneous (s.c.) versus intravenous (i.v.) formulation of rituximab given with chemotherapy in previously untreated patients with CD20+ diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients and methods: Patients received eight cycles of rituximab according to 2 schedules: Arm A received 1 cycle rituximab i.v. (375 mg/m2) and 3 cycles rituximab s.c. (1400 mg) then 4 cycles rituximab i.v.; Arm B received 4 cycles rituximab i.v. (375 mg/m2) then 4 cycles rituximab s.c. (1400 mg). Alongside rituximab, both arms received 6-8 cycles of chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), cyclophosphamide, vincristine, prednisone (CVP), or bendamustine as per standard local practice). Preference for s.c. or i.v. administration was evaluated using the Patient Preference Questionnaire (PPQ) at cycles 6 and 8. Patient satisfaction and convenience were assessed using the Cancer Therapy Satisfaction Questionnaire (CTSQ), and Rituximab Administration Satisfaction Questionnaire (RASQ) at cycles 4 and 8. Results: At the primary data cut-off (19 January 2015), the intent-to-treat population comprised 743 patients. The majority had DLBCL (63%) and baseline characteristics were balanced between arms. At cycle 8, 81% of patients completing the PPQ preferred rituximab s.c. Preference was not impacted by treatment sequence or disease type. Patient satisfaction as measured by RASQ was higher for s.c. versus i.v. CTSQ scores were similar between arms. Adverse events were generally balanced between administration routes and no new safety signals were detected. Conclusion: Most previously untreated patients with CD20+ DLBCL or FL preferred s.c. to i.v. rituximab administration. Patient satisfaction with rituximab treatment was generally greater with s.c. administration. Registered clinical trial number: NCT01724021 (ClinicalTrials.gov).
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Antineoplásicos/administração & dosagem , Linfoma Folicular/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Preferência do Paciente , Rituximab/administração & dosagem , Adulto , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Cross-Over , Feminino , Humanos , Infusões Intravenosas , Infusões Subcutâneas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rituximab/efeitos adversosRESUMO
Wolbachia are intracellular endosymbionts that infect arthropods and filarial nematodes, occasionally causing a wide variety of modifications in host biology, such as male-killing and cytoplasmic incompatibility (CI), amongst others. This study assembled draft genomes for Wolbachia infecting Drosophila incompta, a species that uses flowers as exclusive breeding and feeding sites, in two distinct Brazilian populations. The absence of four genes involved in CI from this genome, together with literature reports of low frequencies of infected flies in wild populations that contain high mitogenome polymorphism, suggests that this bacterium does not induce CI in D. incompta. Phylogenomic analysis placed Wolbachia infecting D. incompta as closely related to the wMel strain which received such name since it was originally detected in Drosophila melanogaster. In addition, phylogenetic analysis using the Wolbachia surface protein gene and five genes used for multilocus sequence typing of Wolbachia found infecting Drosophila and other arthropod species of Old and New World displayed a complex evolutionary scenario involving recent horizontal transfer bursts in all major clades of Wolbachia pipens belonging to the supergroup A in both geographical regions.
Assuntos
Drosophila/microbiologia , Evolução Molecular , Genoma Bacteriano , Wolbachia/genética , Animais , Brasil , Filogenia , Wolbachia/fisiologiaRESUMO
Drosophila incompta belongs to the flavopilosa group of Drosophila, and has a restricted ecology, being adapted to flowers of Cestrum as feeding and oviposition sites. We sequenced, assembled, and characterized the complete mitochondrial genome (mtDNA) of D. incompta. In addition, we performed phylogenomic and polymorphism analyses to assess evolutionary diversification of this species. Our results suggest that this genome is syntenic with the other published mtDNA of Drosophila. This molecule contains 15,641 bp and encompasses two rRNA, 22 tRNA and 13 protein-coding genes. Regarding nucleotide composition, we found a high A-T bias (76.6 %). The recovered phylogenies indicate D. incompta in the virilis-repleta radiation, as sister to the virilis or repleta groups. The most interesting result is the high degree of polymorphism found throughout the D. incompta mitogenome, revealing pronounced intrapopulational variation. Furthermore, intraspecific nucleotide diversity levels varied between different regions of the genome, thus allowing the use of different mitochondrial molecular markers for analysis of population structure of this species.
Assuntos
Drosophila/genética , Genoma de Inseto , Genoma Mitocondrial , Animais , Teorema de Bayes , DNA Mitocondrial/genética , Filogenia , Polimorfismo Genético , Análise de Sequência de DNARESUMO
Background: Electrocardiogram (ECG) has proven to be useful for early detection of cardiac involvement in Anderson-Fabry disease (AFD); however, little evidence is available on the association between ECG alterations and the progression of the disease. Aim and Methods: To perform a cross sectional comparison of ECG abnormalities throughout different left ventricular hypertrophy (LVH) severity subgroups, providing ECG patterns specific of the progressive AFD stages. 189 AFD patients from a multicenter cohort underwent comprehensive ECG analysis, echocardiography, and clinical evaluation. Results: The study cohort (39% males, median age 47 years, 68% classical AFD) was divided into 4 groups according to different degree of left ventricular (LV) thickness: group A ≤ 9â mm (n = 52, 28%); group B 10-14â mm (n = 76, 40%); group C 15-19â mm (n = 46, 24%); group D ≥ 20â mm (n = 15, 8%). The most frequent conduction delay was right bundle branch block (RBBB), incomplete in groups B and C (20%,22%) and complete RBBB in group D (54%, p < 0.001); none of the patients had left bundle branch block (LBBB). Left anterior fascicular block, LVH criteria, negative T waves, ST depression were more common in the advanced stages of the disease (p < 0.001). Summarizing our results, we suggested ECG patterns representative of the different AFD stages as assessed by the increases in LV thickness over time (Central Figure). Patients from group A showed mostly a normal ECG (77%) or minor anomalies like LVH criteria (8%) and delta wave/slurred QR onset + borderline PR (8%). Differently, patients from groups B and C exhibited more heterogeneous ECG patterns: LVH (17%; 7% respectively); LVH + LV strain (9%; 17%); incomplete RBBB + repolarization abnormalities (8%; 9%), more frequently associated with LVH criteria in group C than B (8%; 15%). Finally, patients from group D showed very peculiar ECG patterns, represented by complete RBBB + LVH and repolarization abnormalities (40%), sometimes associated with QRS fragmentation (13%). Conclusions: ECG is a sensitive tool for early identification and long-term monitoring of cardiac involvement in patients with AFD, providing "instantaneous pictures" along the natural history of AFD. Whether ECG changes may be associated with clinical events remains to be determined.
RESUMO
Whereas the signaling function of the interleukin 1 (IL-1) receptor type I (IL-1R I) has been well documented, the type II "receptor" has been suggested to act as a decoy target for this cytokine. Since IL-1 may represent a key target of the immunomodulatory and antiinflammatory properties of glucocorticoids (GC), the aim of this study was to investigate the effects of dexamethasone (Dex) on IL-1R expression in human polymorphonuclear leukocytes (PMN), which express predominantly the type II molecule (IL-1R II). We found that Dex augments the levels of steady state transcripts encoding the IL-1R I and, most prominently, those of IL-1R II. Dex induced both transcripts via transcription-dependent mechanisms and by prolongation of the mRNAs half-lives. Inhibition of protein synthesis superinduced basal and Dex-augmented IL-1R II mRNA, whereas it completely inhibited the induction by Dex of IL-1R I transcripts. Induction of IL-1R II mRNA by Dex was associated with augmented membrane expression and release of the type II IL-1 binding molecule. This effect was mediated by the GC receptor. Other steroids (17 beta-estradiol, progesterone, and testosterone) were ineffective. The concentrations of IL-1 alpha and IL-1 receptor antagonist required to displace the binding of IL-1 beta to the soluble form of the decoy molecule induced by Dex from PMN were, respectively, 100 and 2 times higher compared with IL-1 beta. The induction by Dex of the type II receptor, a decoy molecule for IL-1, may contribute to the immunosuppressive and antiinflammatory activities of Dex.
Assuntos
Dexametasona/farmacologia , Interleucina-1/metabolismo , Neutrófilos/metabolismo , Receptores de Interleucina-1/biossíntese , Meia-Vida , Humanos , Técnicas In Vitro , Ligantes , Neutrófilos/efeitos dos fármacos , RNA Mensageiro/metabolismo , Receptores de Interleucina-1/antagonistas & inibidores , Receptores de Interleucina-1/metabolismo , SolubilidadeRESUMO
The hypothesis that the type II receptor (RII) acts as a decoy for interleukin-1 (IL-1) was tested by gene transfer in cells expressing only the type I receptor (8387 fibroblasts). RII-transfected cells showed defective responsiveness to IL-1 in terms of NFkappaB activation, cytokine gene expression and production. Blocking monoclonal antibodies against RII restored the capacity of RII-transfected cells to respond to IL-1 beta. Hence defective IL-1 responsiveness of RII-transfected cells requires surface expression of the molecule. RII-transfected cells showed normal responsiveness to TNF, which shares functional properties and elements in the signal transduction pathway with IL-1. Cells transfected with a deletion mutant of RII missing 26 of 29 amino acids of the cytoplasmic portion of the molecule showed impaired responsiveness to IL-2. Cells transfected with full-length or the cytoplasmic deletion mutant of RII released copious amounts of RII in the supernatant. However, transfected cells showed defective responsiveness to brief exposure to IL-1, in the absence of measurable released RII. These results indicate that impairment of the responsiveness to IL-1 following RII gene transfer was dependent upon surface expression of the molecule, specific for IL-1 and unaffected by truncation of the cytoplasmic portion. Thus, the type II "receptor" is a decoy surface molecule, regulated by antiinflammatory signals, whose only known function is to capture and block IL-1.
Assuntos
Interleucina-1/antagonistas & inibidores , Interleucina-1/metabolismo , Receptores de Interleucina-1 , Receptores de Interleucina/metabolismo , Transdução de Sinais , Sequência de Bases , Expressão Gênica , Técnicas de Transferência de Genes , Humanos , Modelos Biológicos , Dados de Sequência Molecular , NF-kappa B/metabolismo , Receptores de Interleucina/genética , Receptores Tipo II de Interleucina-1 , TransfecçãoRESUMO
We recently described gammadelta T cells alterations in patients with a cutaneous primary melanoma. To evaluate whether gammadelta T cells alterations persisted after melanoma removal, we performed a follow-up study comparing the number and function of gammadelta T lymphocytes from 19 subjects, 4 years after the removal of a cutaneous primary melanoma, with the data obtained in the same subjects before the surgical intervention and with control donors. The number of circulating gammadelta(+) T cells after melanoma removal was not recovered to the levels found in controls. gammadelta(+) T cells producing TNF-alpha or IFN-gamma were increased after melanoma removal in comparison with the same subjects before surgical intervention or with control donors. After in vitro culture, both the percentage and the expansion of gammadelta T cells were recovered to the values found in controls. In conclusion, the functional capacity of gammadelta T cells was in vitro recovered after melanoma removal, whereas their ex vivo number remained at lower levels than control donors.
Assuntos
Melanoma/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Neoplasias Cutâneas/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Técnicas In Vitro , Interferon gama/sangue , Interferon gama/imunologia , Modelos Lineares , Ativação Linfocitária/imunologia , Contagem de Linfócitos , Melanoma/sangue , Melanoma/cirurgia , Pessoa de Meia-Idade , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/cirurgia , Linfócitos T/citologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologiaRESUMO
When cultivated on substrates that prevent cell adhesion (the polymer polyhydroxyethylmethacrylate, bovine serum albumin, and Teflon), human endothelial cells (EC) rapidly lost viability with a half-life of approximately 10 h. Dying EC showed the morphological and biochemical characteristics of apoptosis. The apoptotic process of suspended EC was delayed by the protein synthesis inhibitor cycloheximide. To obtain information as to the mechanism involved in the apoptosis of suspended EC, we investigated whether adhesion to matrix proteins or integrin occupancy in EC retaining a round shape may affect EC suicide. EC bound to low coating concentration of either fibronectin or vitronectin, retaining a round shape and failing to organize actin microfilaments, underwent to rapid cell death; by contrast, cells on high substrate concentrations became flattened, showed actin microfilament organization, and retained viability. Addition of saturating amounts of soluble vitronectin to suspended round-shaped EC did not reduce the process of apoptosis. Finally, when suspended EC bound Gly-Arg-Gly-Asp-Ser-coated microbeads (approximately 10 microbeads/cell), yet retaining a round shape, the apoptotic process was not affected. Oncogene-transformed EC in suspension were less susceptible to cell death and apoptosis than normal EC. Overall, these data indicate that cell attachment to matrix or integrin binding per se is not sufficient for maintaining cell viability, and that cells need to undergo some minimal degree of shape change to survive. Modulation of interaction with the extracellular matrix can, therefore, be an important target for the control of angiogenesis.
Assuntos
Apoptose , Endotélio Vascular/citologia , Matriz Extracelular/metabolismo , Sequência de Aminoácidos , Adesão Celular , Movimento Celular , Tamanho Celular , Sobrevivência Celular , Transformação Celular Neoplásica , Células Cultivadas , Cicloeximida/farmacologia , Fibronectinas/metabolismo , Glicoproteínas/metabolismo , Humanos , Dados de Sequência Molecular , Oligopeptídeos/metabolismo , VitronectinaRESUMO
Interleukin-1 (IL-1) interacts with cells through two types of binding molecules, IL-1 type I receptor (IL-1R I) and IL-1R II. The function of IL-1R II is unknown. In studies using monoclonal antibodies, IL-1 prolonged the in vitro survival of polymorphonuclear cells (PMN) through IL-1R I, and IL-4 antagonized the action of IL-1 by inducing expression and release of IL-1R II. Dexamethasone also induced expression and release of the IL-1R II in PMN. These results, together with the effect of antibodies to IL-1R on IL-1-induced production of cytokines in monocytes, indicate that IL-1 acts on myelomonocytic cells through IL-1R I and that IL-1R II inhibits IL-1 activity by acting as a decoy target for IL-1. The existence of multiple pathways of regulation emphasizes the need for tight control of IL-1 action.
Assuntos
Interleucina-1/fisiologia , Interleucina-4/fisiologia , Neutrófilos/fisiologia , Receptores de Interleucina-1/fisiologia , Anticorpos Monoclonais , Sobrevivência Celular/imunologia , Dexametasona/farmacologia , Humanos , Técnicas In Vitro , Peso Molecular , Monócitos/fisiologia , Receptores de Interleucina-1/classificação , Receptores de Interleucina-1/efeitos dos fármacosRESUMO
BACKGROUND: Carfilzomib, a proteasome inhibitor, known as a therapeutical option for people who have already received one or more previous treatments for multiple myeloma, has well known cardiac and systemic adverse effects. OBJECTIVE: There is evidence supporting that adverse effects are dose dependent, yet there is no known patient phenotype characterized by worse associated consequences, nor are there widely accepted monitoring protocols. RESULTS: In this article we describe two patients with cardiovascular adverse events related to carfilzomib treatment and their clinical course. Our goal was to present two cases of daily practice, which highlighted the complexity of their management and led to underline how baseline evaluation and close follow-up with echocardiography and cardiac biomarkers, including natriuretic peptides, remain an important tool for the cardiotoxicity surveillance. CONCLUSION: These reflections should lead to further studies in order to identify high risk patients for cardiovascular adverse event and clarify the real incidence of cardiotoxicity of this drug and adequate follow-up timing. Finally further research is needed to evaluate strategies for prevention and attenuation of cardiovascular complications of cancer therapy.
Assuntos
Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Cardiopatias/induzido quimicamente , Mieloma Múltiplo/tratamento farmacológico , Oligopeptídeos/efeitos adversos , Idoso , Antineoplásicos/uso terapêutico , Cardiotoxicidade/terapia , Feminino , Cardiopatias/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/uso terapêutico , Inibidores de Proteassoma/efeitos adversos , Inibidores de Proteassoma/uso terapêuticoRESUMO
Acute myocardial infarction, pulmonary embolism, and aortic dissection are diseases associated with acute chest pain and may lead to severe morbidity and mortality. These diseases may not be trivial to diagnose in the settings of emergency room. ECG-gated multi-detector computed tomography (MDCT), already established for the assessment of pulmonary embolism and aortic dissection, provides reliable information regarding the triage of patients with acute coronary syndrome in the emergency room. MDCT recently appeared to be logistically feasible and a promising comprehensive method for the evaluation of cardiac and non-cardiac chest pain in emergency department patients. The possibility to scan the entire thorax visualizing the thoracic aorta, the pulmonary arteries, and the coronary arteries could provide a new approach to the triage of acute chest pain. The inherent advantage of MDCT with cardiac state-of-the-art capabilities is the rapid investigation of the main sources of acute chest pain with a high negative predictive value. Recent studies also reports an advantage in terms of costs. With current evidence, the selection of patients with acute chest pain candidates to MDCT should remain restricted to avoid unjustified risk of ionizing radiation.
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Angina Instável/diagnóstico por imagem , Dor no Peito/diagnóstico por imagem , Cuidados Críticos/métodos , Eletrocardiografia/métodos , Infarto do Miocárdio/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Intensificação de Imagem Radiográfica/instrumentação , Síndrome , Tomografia Computadorizada por Raios X/instrumentaçãoRESUMO
Solid lipid nanoparticles (SLN) are colloidal drug delivery systems characterized by higher entrapment efficiency, good scalability of the preparation process and increased sustained prolonged release of the payload compared to other nanocarriers. The possibility to functionalize the surface of SLN with ligands to achieve a site specific targeting makes them attractive to overcome the limited blood-brain barrier (BBB) penetration of therapeutic compounds. SLN are prepared for brain targeting by exploiting the adaptability of warm microemulsion process for the covalent surface modification with an Apolipoprotein E-derived peptide (SLN-mApoE). Furthermore, the influence of the administration route on SLN-mApoE brain bioavailability is here evaluated. SLN-mApoE are able to cross intact a BBB in vitro model. The pulmonary administration of SLN-mApoE is related to a higher confinement in the brain of Balb/c mice compared to the intravenous and intraperitoneal administration routes, without inducing any acute inflammatory reaction in the lungs. These results promote the pulmonary administration of brain-targeted SLN as a feasible strategy for improving brain delivery of therapeutics.
Assuntos
Apolipoproteínas E/metabolismo , Barreira Hematoencefálica/metabolismo , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos , Nanopartículas/metabolismo , Animais , Apolipoproteínas E/química , Apolipoproteínas E/farmacocinética , Células 3T3 BALB , Permeabilidade Capilar , Linhagem Celular , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Metabolismo dos Lipídeos , Lipídeos/química , Lipídeos/farmacocinética , Masculino , Camundongos , Nanopartículas/química , Propriedades de SuperfícieRESUMO
We assessed mammaglobin (MMG) gene expression in bone marrow (BM) aspirates from patients with advanced breast cancer who had received a reduced-intensity conditioning and stem cell allografting, in order to detect a graft-versus-tumor effect on micrometastatic disease. Nine patients received a reduced-intensity conditioning with fludarabine, cyclophosphamide, and thiotepa, followed by peripheral blood allografting from HLA-identical sibling donors. Nested RT-PCR analysis with sequence-specific primers for MMG was carried out on a monthly basis on BM samples. Three patients had MMG-positive BM, four patients had MMG-negative BM before allografting, and two were undetermined. In two patients, a clinical response after allografting (partial remission) occurred concurrently with the clearance of MMG expression, at a median of 6 months after allografting, following immune manipulation. In two patients, a prolonged stable disease and negative MMG expression occurred after day +360 from allografting. In two patients, progression of the disease was associated with MMG RT-PCR changing from negative to positive. In one case, a disease response occurring after donor lymphocyte infusion and grade II acute GVHD was heralded by negativization of MMG expression. Although preliminary, these data suggest that a graft-versus-breast cancer effect is detectable on micrometastatic BM disease.
Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias da Medula Óssea/metabolismo , Medula Óssea/metabolismo , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Efeito Enxerto vs Tumor , Proteínas de Neoplasias/biossíntese , Uteroglobina/biossíntese , Adulto , Medula Óssea/patologia , Neoplasias da Medula Óssea/patologia , Neoplasias da Medula Óssea/secundário , Neoplasias da Medula Óssea/terapia , Transplante de Medula Óssea , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Ciclofosfamida/administração & dosagem , Feminino , Sobrevivência de Enxerto , Humanos , Mamoglobina A , Pessoa de Meia-Idade , Agonistas Mieloablativos/administração & dosagem , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Tiotepa/administração & dosagem , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
A total of 96 tumour samples (88 primary tumours and 8 nodal metastases) from 88 patients with thyroid adenomas and carcinomas were investigated for ras gene mutations using polymerase chain reaction, oligonucleotide probing and sequencing. Neither the 19 adenomas nor the 31 papillary carcinomas analysed harboured point mutations. In our cases, mutations in all three ras oncogenes were found in follicular carcinomas (five out of 21) and in the less differentiated thyroid tumour: poorly differentiated carcinomas (three out of 11) and undifferentiated carcinomas (one out of five). Finally, mutated ras oncogenes had a significant association with the appearance of haematogenous (particularly bone) metastases, suggesting a role of ras genes activation in the metastatic capability of these tumours.
Assuntos
Adenocarcinoma Folicular/genética , Carcinoma Papilar/genética , Genes ras/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/secundário , Sequência de Bases , Carcinoma Papilar/secundário , Análise Mutacional de DNA , Humanos , Dados de Sequência Molecular , Oncogenes , Mutação Puntual , Reação em Cadeia da Polimerase , Neoplasias da Glândula Tireoide/secundárioRESUMO
The experience of the Istituto Nazionale Tumori of Milan on dysgerminoma is presented. Between 1970 and December of 1982, 25 patients were treated with a unique protocol which considered surgery and radiotherapy with different schedules according to the extension of the disease. With this treatment protocol all 13 patients at Stage I were alive and free of disease with a median follow-up of 77 months. Of 12 patients at Stage III (10 retroperitoneal and 2 retroperitoneal and peritoneal) 4 relapsed. The 5-year relapse-free survival of Stage III patients was 61.4% and the overall survival 89.5%. Amenorrhea due to radiation dose absorbed by the contralateral shielded ovary was found in 7.7%. The excellent results in Stage I patients were balanced by the unsatisfactory results in Stage III patients. A more aggressive treatment and the knowledge of other prognostic factors seem necessary.