RESUMO
BACKGROUND AND PURPOSE: Stereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS. MATERIALS AND METHODS: This is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity. RESULTS: From 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %. CONCLUSION: SABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years.
Assuntos
Radiocirurgia , Sarcoma , Adulto , Humanos , Radiocirurgia/efeitos adversos , Intervalo Livre de Progressão , Oncologia , Sarcoma/radioterapia , Itália , Estudos RetrospectivosRESUMO
Squamous cervical carcinoma (SCC) requires particular attention in diagnostic and clinical management. New diagnostic tools, such as (positron emission tomography-magnetic resonance imaging) PET-MRI, consent to ameliorate clinical staging accuracy. The availability of new technologies in radiation therapy permits to deliver higher dose lowering toxicities. In this clinical scenario, new surgical concepts could aid in general management. Lastly, new targeted therapies and immunotherapy will have more room in this setting. The aim of this narrative review is to focus both on clinical management and new therapies in the precision radiotherapy era.
Assuntos
Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Tomografia por Emissão de Pósitrons , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Quimiorradioterapia/métodos , Estadiamento de NeoplasiasRESUMO
AIM: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) for spine oligometastases. MATERIALS AND METHODS: This was a multicentre retrospective study of a series of patients who received SBRT for spine oligometastases. The efficacy of SBRT was evaluated in terms of local control as the primary endpoint. Survival outcomes were also analysed to identify predictive factors for clinical outcomes. Toxicity was assessed according to CTCAE v4.0. RESULTS: Between March 2018 and July 2022, 183 lesions in 177 patients were analysed. In most patients, SBRT was delivered to a single spine metastasis (82%) for a median total dose of 21 Gy (14-35 Gy) in three fractions (one to five fractions) and a median BED10 = 119 Gy (57.7-152 Gy). Local control rates were 90.3% at 1 year, 84.3% at 2 years and 84.3% at 3 years. Distant progression-free survival rates were 33.1%, 18.5% and 12.4% at 1, 2 and 3 years, with prostate histology (P = 0.023), oligorecurrent disease (P = 0.04) and BED10 > 100 Gy (P = 0.04) found to be predictive on univariate analysis. A further oligometastatic progression was observed in 33 patients (18.6%) treated with a second course of SBRT, reporting at univariate analysis improved overall survival rates (P = 0.01). Polymetastases-free survival rates were 57.8%, 43.4% and 32.4%; concurrent therapy was related to improved outcomes at multivariate analysis (P = 0.009). Overall survival rates were 91.8%, 79.6% and 65.9%, with prostate histology and non-cervical metastases related to better overall survival at multivariate analysis. Pain-flare after SBRT was recorded in 3.3%; five patients underwent surgical decompression after SBRT; there were no grade ≥3 adverse events. CONCLUSIONS: In our experience of only oligometastatic patients, spine SBRT gave excellent results in terms of safety and efficacy. Prostate histology and oligorecurrent disease were predictive factors for improved clinical outcomes; also, patients who experienced a further oligoprogression after SBRT maintained a survival advantage compared with polymetastatic progression. No severe adverse events were reported.
Assuntos
Radiocirurgia , Masculino , Humanos , Radiocirurgia/métodos , Estudos Retrospectivos , Intervalo Livre de Progressão , Taxa de Sobrevida , OncologiaRESUMO
BACKGROUND: Stereotactic Ablative Radiotherapy (SABR) is an effective treatment that improves local control for many tumours. However, the role of SABR in gynecological cancers (GYN) has not been well-established. We hypothesize that there exists considerable variation in GYN-SABR practice and technique. The goal of this study is to describe clinical and technical factors in utilization of GYN-SABR among 11 experienced radiation oncologists. MATERIALS AND METHODS: A 63 question survey on GYN-SABR was sent to 11 radiation oncologists (5 countries) who have published original research, conducted trials or have an established program at their institutions. Responses were combined and analyzed at a central institution. RESULTS: Most respondents indicated that salvage therapy (non-irradiated or re-irradiated field) for nodal (81%) and primary recurrent disease (91%) could be considered standard options for SABR in the setting of inability to administer brachytherapy. All other indications should be considered on clinical trials. Most would not offer SABR as a boost in primary treatment off-trial without absolute contraindications to brachytherapy. Multi-modality imaging is often (91%) used for planning including PET, CT contrast and MRI. There is a wide variation for OAR tolerances however small bowel is considered the dose-limiting structure for most experts (91%). Fractionation schedules range from 3 to 6 fractions for nodal/primary definitive and boost SABR. CONCLUSIONS: Although SABR has become increasingly standard in other oncology disease sites, there remains a wide variation in both clinical and technical factors when treating GYN cancers. Nodal and recurrent disease is considered a potential indication for SABR whereas other indications should be offered on clinical trials. This study summarizes SABR practices among GYN radiation oncologists while further studies are needed to establish consensus guidelines for GYN-SABR treatment.
Assuntos
Neoplasias dos Genitais Femininos/radioterapia , Padrões de Prática Médica/estatística & dados numéricos , Radiocirurgia/estatística & dados numéricos , Fracionamento da Dose de Radiação , Feminino , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Neoplasias dos Genitais Femininos/patologia , Humanos , Metástase Linfática , Imagem Multimodal , Recidiva Local de Neoplasia , Órgãos em Risco/efeitos da radiação , Radio-Oncologistas/estatística & dados numéricos , Planejamento da Radioterapia Assistida por Computador , Terapia de Salvação , Inquéritos e QuestionáriosRESUMO
The activity and circulation of influenza viruses in Argentina was studied during 2012 as part of the Argentinean Surveillance for Influenza and other Respiratory Viruses, in the context of Global Influenza Surveillance. The antigenicity and molecular characteristics of haemagglutinins (HA) of circulating influenza A and B viruses were analysed to assess the emergence of virus variants. Susceptibility to oseltamivir and zanamivir was evaluated by enzymatic assay and results were backed-up by sequencing of the neuraminidase (NA) genes. During the 2012 season, influenza virus circulation in Argentina was detected from weeks 24 to 51. The HA sequences of the studied A(H1N1)pdm09 subtype viruses segregated in a different genetic group compared to those identified during the 2009 pandemic, although they were still closely related antigenically to the vaccine virus A/California/07/2009. The HA sequences of the A(H3N2) viruses analysed fell into the A/Victoria/208/2009 clade, genetic group 3C. A mixed circulation of virus variants belonging to B/Victoria and B/Yamagata lineages was detected, with B/Victoria being dominant. All viruses tested were sensitive to oseltamivir and zanamivir except one. This isolate, an A(H1N1)pdm09 virus possessing the substitution NA-N295S, showed highly reduced inhibition by oseltamivir and reduced inhibition by zanamivir. Virological and epidemiological surveillance remains critical for detection of evolving influenza viruses.
Assuntos
Antivirais/farmacologia , Farmacorresistência Viral , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Influenza Humana/epidemiologia , Vigilância da População , Argentina/epidemiologia , Hemaglutininas/genética , Hemaglutininas/metabolismo , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Vírus da Influenza A/fisiologia , Vírus da Influenza B/genética , Vírus da Influenza B/imunologia , Vírus da Influenza B/fisiologia , Influenza Humana/virologia , Neuraminidase/genética , Neuraminidase/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
BACKGROUND: Stereotactic body radiotherapy (SBRT) can emulate high dose rate brachytherapy (HDR-BRT) dose fractionation. We report our preliminary results using SBRT in monotherapy or pre-external-beam radiotherapy (EBRT) boost in patients with localized prostate cancer (LpC). The primary end point was the evaluation of both acute and late toxicities; secondary end point was the observation of prostate-specific antigen (PSA) nadir. PATIENTS AND METHODS: Patients with LpC having prostate volume ≤90 cm(3) were enrolled in the present study. Patients were treated with SBRT alone or in combined modality (SBRT + EBRT). SBRT was performed using a CyberKnife System (Accuray Incorporated, Sunnyvale, California) and fiducial tracking system. RESULTS: From February 2008 to July 2013, 21 patients for monotherapy (38 Gy/4 fractions) and 5 for combined modality (9.5 Gy/2 fractions plus 46 Gy/23 fractions EBRT) were enrolled. Androgen deprivation therapy (ADT) was administered in 16 of the 26 patients. The median pretreatment PSA was 9.4 (range, 4.5-14.3) ng/mL. All patients completed the planned therapy. Acute Grade 1 toxicity was observed in 18 patients, genitourinary (GU) in 12 / 26 patients, and gastrointestinal (GI) in 6 / 26 patients. Acute Grade 2 GU toxicity was reported in 1 / 26 patients, and Grade 2 GI toxicity was observed in 2 / 26 patients. The median PSA nadir was 0.15 (range, 0.02 = 1.4) ng/mL. Late toxicities were observed in 5 / 26 patients: Grade 1 GU (3 of 26), Grade 2 GU (1 of 26), and Grade 1 GI (1 of 26). Median follow-up was 21.5 (range, 8-65) months. CONCLUSIONS: Our preliminary results of SBRT "simulating" HDR for LpC confirm a minimal toxicity and an optimal PSA response. The PSA nadirs appear comparable with HDR-BRT.
Assuntos
Adenocarcinoma/cirurgia , Neoplasias da Próstata/cirurgia , Radiocirurgia , Adenocarcinoma/sangue , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Seguimentos , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Planejamento da Radioterapia Assistida por Computador , Robótica , Cirurgia Assistida por Computador , Resultado do TratamentoRESUMO
BACKGROUND: During pregnancy, immunological and hormonal alterations place women at increased risk for influenza-related severe illnesses including hospitalization and death. Although A(H1N1) pdm09 infection resulted in increased disease severity in pregnant women, the precise mechanisms responsible for this risk have yet to be established. OBJECTIVES: The present study was aimed to investigate the role of host chemokines and cytokine profiles in A(H1N1) pdm09 infection regarding disease severity in pregnant women. STUDY DESIGN: This retrospective survey examined 41 pregnant women with confirmed A(H1N1) pdm09 infection. Of them, 12 died (D), 29 survived (S), and 17 remained uninfected and served as controls (C). Antiviral response was evaluated for IFN-ß expression and gene expression profiles of cytokines (TNF-α, IL-6, IL-12, TGF-ß) and chemokines (IL-8, RANTES, MCP-1, IP-10), and the viral Matrix (M1) gene was quantified and normalized using the housekeeping gene product ß-actin mRNA. RESULTS: Higher IL-8 and TNF-α mRNA expression were found in D and S compared with C, while IL-6 showed higher expression in D. Interestingly, these results were associated with a decrease in the anti-inflammatory response of TGF-ß mRNA and IFN-ß. These alterations would lead to an imbalance in the immune response of those patients. CONCLUSIONS: Pregnancy-related reductions in IFN-ß and TGF-ß expression levels and elevated levels of pro-inflammatory cytokines could explain the increased severity of infection and death of pregnant women. These findings may help improve the understanding of the high susceptibility and disease severity to influenza virus infection during pregnancy.
Assuntos
Quimiocinas/genética , Citocinas/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/imunologia , Complicações Infecciosas na Gravidez/imunologia , Adulto , Quimiocinas/imunologia , Quimiocinas/isolamento & purificação , Citocinas/imunologia , Citocinas/isolamento & purificação , Feminino , Perfilação da Expressão Gênica , Humanos , Influenza Humana/mortalidade , Influenza Humana/virologia , Interferon beta/genética , Interferon beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Gravidez , Complicações Infecciosas na Gravidez/mortalidade , Estudos Retrospectivos , Índice de Gravidade de Doença , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/imunologia , Fator de Necrose Tumoral alfa/genéticaRESUMO
The prevalence of genetic polymorphisms identified as predictors of therapeutic-induced hepatitis C virus (HCV) clearance differs among ethnic groups. However, there is a paucity of information about their prevalence in South American populations, whose genetic background is highly admixed. Hence, single-nucleotide polymorphisms rs12979860, rs1127354 and rs7270101 were characterized in 1350 healthy individuals, and ethnicity was assessed in 259 randomly selected samples. The frequency of rs12979860CC, associated to HCV treatment response, and rs1127354nonCC, related to protection against hemolytic anemia, were significantly higher among individuals with maternal and paternal Non-native American haplogroups (64.5% and 24.2%), intermediate among admixed samples (44.1% and 20.4%) and the lowest for individuals with Native American ancestry (30.4% and 6.5%). This is the first systematic study focused on analyzing HCV predictors of antiviral response and ethnicity in South American populations. The characterization of these variants is critical to evaluate the risk-benefit of antiviral treatment according to the patient ancestry in admixed populations.
Assuntos
Antivirais/farmacologia , Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Polimorfismo de Nucleotídeo Único/genética , Etnicidade/genética , Genótipo , Hepatite C Crônica/virologia , Humanos , Medição de Risco , América do SulRESUMO
Influenza virus (InfV) infection during pregnancy is a known risk factor for neurodevelopment abnormalities in the offspring, including the risk of schizophrenia, and has been shown to result in an abnormal behavioral phenotype in mice. However, previous reports have concentrated on neuroadapted influenza strains, whereas increased schizophrenia risk is associated with common respiratory InfV. In addition, no specific mechanism has been proposed for the actions of maternal infection on the developing brain that could account for schizophrenia risk. We identified two common isolates from the community with antigenic configurations H3N2 and H1N1 and compared their effects on developing brain with a mouse modified-strain A/WSN/33 specifically on the developing of dopaminergic neurons. We found that H1N1 InfV have high affinity for dopaminergic neurons in vitro, leading to nuclear factor kappa B activation and apoptosis. Furthermore, prenatal infection of mothers with the same strains results in loss of dopaminergic neurons in the offspring, and in an abnormal behavioral phenotype. We propose that the well-known contribution of InfV to risk of schizophrenia during development may involve a similar specific mechanism and discuss evidence from the literature in relation to this hypothesis.
Assuntos
Encéfalo/virologia , Neurônios Dopaminérgicos/virologia , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Infecções por Orthomyxoviridae/virologia , Efeitos Tardios da Exposição Pré-Natal/virologia , Esquizofrenia/virologia , Animais , Comportamento Animal/fisiologia , Encéfalo/imunologia , Encéfalo/fisiopatologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Aprendizagem em Labirinto/fisiologia , Camundongos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Reconhecimento Psicológico/fisiologiaRESUMO
Cerebral arteriovenous malformations (AVMs) represent congenital anomalies of blood vessels composed of a nidus of anomalous arterial and venous vessels without a capillary network. We describe a case of bleeding cerebral AVM in a pregnant women at the second quarter of gestation and diagnosed by digital subtraction angiography showing a large principal arterial nidus supply. The AVM was treated by endovascular embolization at the 27th week of gestation. The post-operative course was uneventful and a caesarean section was performed at the 37th week of gestation. The endovascular approach may represent a safe method in the treatment of this cerebral condition during pregnancy.
RESUMO
A dramatic rise in the frequency of resistance to adamantane drugs by influenza A H3 viruses, associated with a single amino acid replacement in the viral matrix M2 protein, has occurred in multiple countries worldwide in recent years. We investigated the frequency of adamantane-resistant influenza A H3 viruses in Argentina during the period 2001-2007. We used reverse transcription followed by polymerase chain reaction. The obtained products were sequenced for the detection of mutations of the M2 gere relevant to the resistance phenotypes. The HA1 sequences of the sensitive and resistant strains were also analyzed to clarify whether they had any relevance to the resistant mutations. Twenty out of 55 (36%) strains were identified with the resistance-conferring substitution at amino acid 31 (Serine 31 Asparagine). No resistant viruses were detected between 2001 and 2005. All strains isolated in 2006 and four out of five isolates from 2007 were resistant. None of the patients had received previous treatment with amantadine and/or rimantadine. The HA1 analysis showed that there were only two changes (Serine193 Phenylalanine and Aspartic acid 225 Asparagine) present in the strains with the M2 substitution at position 31. Our data indicate that since 2006 there has been a significant increase of adamantane-resistant influenza A H3 viruses, which raises concern over the spread of these viruses in Argentina.
Assuntos
Adamantano/farmacologia , Farmacorresistência Viral , Vírus da Influenza A/efeitos dos fármacos , Argentina , Humanos , Vírus da Influenza A/isolamento & purificação , Fatores de TempoRESUMO
A dramatic rise in the frequency of resistance to adamantane drugs by influenza A H3 viruses, associated with a single amino acid replacement in the viral matrix M2 protein, has occurred in multiple countries worldwide in recent years. We investigated the frequency of adamantane-resistant influenza A H3 viruses in Argentina during the period 2001- 2007. We used reverse transcription followed by polymerase chain reaction. The obtained products were sequenced for the detection of mutations of the M2 gene relevant to the resistance phenotypes. The HA1 sequences of the sensitive and resistant strains were also analyzed to clarify whether they had any relevance to the resistant mutations. Twenty out of 55 (36%) strains were identified with the resistance-conferring substitution at amino acid 31 (Serine 31 Asparagine). No resistant viruses were detected between 2001 and 2005. All strains isolated in 2006 and four out of five isolates from 2007 were resistant. None of the patients had received previous treatment with amantadine and/or rimantadine. The HA1 analysis showed that there were only two changes (Serine193 Phenylalanine and Aspartic acid 225 Asparagine) present in the strains with the M2 substitution at position 31. Our data indicate that since 2006 there has been a significant increase of adamantane-resistant influenza A H3 viruses, which raises concern over the spread of these viruses in Argentina.
En los últimos años, se ha detectado un aumento de virus influenza A H3 resistentes a los adamantanos en distintos países, asociados mayoritariamente con el reemplazo de un único aminoácido de la proteína matriz M2. Se investigó la frecuencia de virus influenza A H3 resistentes a los adamantanos en Argentina entre 2001 y 2007. Se utilizó la transcripción reversa seguida de la reacción en cadena de la polimerasa y de la técnica de secuencia directa para la detección de mutaciones en el gen que codifica para la proteína M2, relevantes para los fenotipos de resistencia. También se analizó la secuencia de la porción HA1 de cepas resistentes y sensibles, para intentar establecer alguna relación con las mutaciones de M2. De un total de 55 cepas, 20 (36%) fueron resistentes debido a un cambio aminoacídico en la posición 31 (serina 31 asparagina). No se detectaron cepas resistentes entre 2001 y 2005. Las cepas aisladas en el 2006 y 4 de 5 cepas obtenidas en el 2007 fueron resistentes. Ninguno de los pacientes de los que se habían aislado esas cepas había recibido tratamiento antiviral con anterioridad. En la porción secuenciada de HA1 se encontraron dos cambios (serina 193 fenilalanina y ácido aspártico 225 asparagina), presentes sólo en las cepas que tuvieron la mutación en la posición 31 de M2. Desde el año 2006 se ha registrado en Argentina un aumento significativo de la circulación de virus influenza A H3 con genotipo resistente, lo que genera expectativa con respecto a su diseminación en nuestro país.
Assuntos
Humanos , Adamantano/farmacologia , Farmacorresistência Viral , Vírus da Influenza A/efeitos dos fármacos , Argentina , Vírus da Influenza A/isolamento & purificação , Fatores de TempoRESUMO
BACKGROUND: Human influenza infections are a significant cause of morbidity worldwide. Though damage to the respiratory epithelium and has been related to apoptosis, which occurs subsequent to influenza virus infection, little information is available regarding cell cytotoxicity of human strains. OBJECTIVE: To study cytotoxicity performed in vitro by various circulating strains in Argentina. The study sample consisted of three vaccine strains (H1N1, H3N2, and B) administered during 1999-2000 in South America and three strains isolated from clinical samples, one, NAC (H1N1) obtained from an adult inpatient with human pneumonia; and the other two (T) and (T2) (H3N2) with influenza syndrome. Viral antigen was detected by an immunofluorescence test, conducted prior to viral isolation in MDCK cells. Strains were subtyped by the hemmaglutination inhibition test. Cytotoxic properties were determined by lactate dehydrogenase reaction (LDH), crystal violet staining and Hoechst staining. Caspase-3 activity, morphological changes of apoptosis, and viral yields were measured in MDCK infected cells. RESULTS AND CONCLUSIONS: Cells infected by each of the strains exhibited apoptosis morphology by Hoechst staining and caspase-3 activity was high for both H1N1 strains. Further, high levels of LDH activity were detected for NAC and H3N2 strains tested, indicating the possible role of different viral proteins or functions on cell cytotoxicity. The NAC strain, isolated from human pneumonia and antigenically related to A/New Caledonia /20/99 (H1N1), was the highest cytotoxic strain and an excellent inducer of caspase-3 activity. In turn, no parameter was related to different viral yields. We conclude that human strains studied in this paper may be useful tools in the characterization of molecular determinants involved in viral cytopathogenicity.
Assuntos
Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/patogenicidade , Vírus da Influenza B/isolamento & purificação , Vírus da Influenza B/patogenicidade , Influenza Humana/virologia , Adulto , Animais , Argentina , Caspase 3 , Caspases/biossíntese , Linhagem Celular , Citotoxicidade Imunológica , Cães , Indução Enzimática , Humanos , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Especificidade da Espécie , Cultura de VírusRESUMO
BACKGROUND: The telomeric-repeat binding factor (TRF1) participates in a physiological homeostatic mechanism controlling telomere shortening by inhibiting telomerase activity: down-regulation of TRF1 expression results in telomere elongation and may be involved in cell immortalization. PATIENTS AND METHODS: To determine the TRF1 expression by immunohistochemistry (IHC) in human brain tumors, a cohort of 20 consecutive flash-frozen surgical specimens (14 meningiomas and 6 anaplastic astrocytomas (AA)) were collected. RESULTS: Variable levels of TRF1 expression in 12 out of the 14 (87.5%) meningioma samples were observed. By contrast, no expression of TRF1 in tissue samples from AA (p = 0.008) was detected. Positive TRF1 cells were usually more differentiated (less atypical features) and Ki67 negative (inverse statistical association, chi2 = p < 0.001). CONCLUSION: We demonstrated, for the first time, that routine IHC techniques are capable of identifying TRF1 expression in intracranial tumors, which is heterogeneously expressed in meningiomas, but absent in AA. Although these preliminary observations need confirmation from larger studies, the TRF1 status in intracranial tumors might become of prognostic value.
Assuntos
Neoplasias Encefálicas/metabolismo , Proteínas de Ligação a DNA/biossíntese , Neoplasias Encefálicas/patologia , Estudos de Viabilidade , Humanos , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Meningioma/metabolismo , Meningioma/patologia , Proteína 1 de Ligação a Repetições TeloméricasRESUMO
OBJECTIVE: Due to the lack of correlation from 1994 to 1997 between the A H3N2 component of the influenza vaccine recommended for this period and the circulating viruses in Argentina, we decided to study the antigenic and genomic relationships of the 1998 A H3N2 Argentine circulating strains with the corresponding vaccine component for that year as recommended by the World Health Organization (WHO). METHODS: We selected 18 influenza A H3N2 strains isolated in Argentina during 1998 to carry out an antigenic and genomic study of their hemagglutinin (HA) and neuraminidase (NA) proteins. For the genomic study we added 3 isolates from Uruguay. We compared the Argentine and Uruguayan strains with available reference strains. RESULTS: We found that all 18 strains from Argentina were similar to the A/Sydney/5/97 (H3N2) strain, as opposed to the A/Wuhan/359/95 (H3N2) strain, which was the vaccine component. This result was confirmed by the genomic study. CONCLUSIONS: The approach that we applied in Argentina has improved the quality and quantity of information about influenza in the country. This type of work should be encouraged in other countries in order to help choose the most appropriate vaccine components each year and provide individuals with the best possible protection against influenza.
Assuntos
Antígenos Virais/análise , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Argentina , Genoma Viral , Hemaglutininas/genética , Humanos , Vacinas contra Influenza , Neuraminidase/genética , Filogenia , UruguaiRESUMO
The clinical or epidemiological influenza diagnosis require fast, sensitive and accessible techniques for small laboratories. In order to investigate the sensitivity of the methods currently used in Argentina, the rapid diagnosis by indirect immunofluorescent assay (IF) was compared to the rapid viral culture in MDCK cells. The diagnosis of influenza virus infection was performed on 81 nasal and pharyngeal swabs collected from outpatients with upper respiratory infection, influenza-like syndrome. The samples were collected during 1998 winter season and both techniques were tested. The IF specificity and sensitivity obtained were 91.9% and 59.5%, respectively. In the selection of the assay to be used for influenza diagnosis, the limitations of the simplest techniques such as IF should be considered. Furthermore, it is advisable to set up an optimized culture method in complex laboratories since culture is the only technique which allows the reference centers to perform the full characterization of the isolates.
Assuntos
Anticorpos Antivirais/análise , Técnica Indireta de Fluorescência para Anticorpo , Vírus da Influenza A/isolamento & purificação , Influenza Humana/diagnóstico , Cavidade Nasal/virologia , Faringe/virologia , Cultura de Vírus , Adulto , Animais , Argentina/epidemiologia , Linhagem Celular , Efeito Citopatogênico Viral , Cães , Cobaias , Testes de Hemaglutinação , Humanos , Vírus da Influenza A/imunologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Pessoa de Meia-Idade , Medicina do Trabalho , Estações do Ano , Sensibilidade e Especificidade , Fatores de TempoRESUMO
The clinical or epidemiological influenza diagnosis require fast, sensitive and accessible techniques for small laboratories. In order to investigate the sensitivity of the methods currently used in Argentina, the rapid diagnosis by indirect immunofluorescent assay (IF) was compared to the rapid viral culture in MDCK cells. The diagnosis of influenza virus infection was performed on 81 nasal and pharyngeal swabs collected from outpatients with upper respiratory infection, influenza-like syndrome. The samples were collected during 1998 winter season and both techniques were tested. The IF specificity and sensitivity obtained were 91.9 and 59.5, respectively. In the selection of the assay to be used for influenza diagnosis, the limitations of the simplest techniques such as IF should be considered. Furthermore, it is advisable to set up an optimized culture method in complex laboratories since culture is the only technique which allows the reference centers to perform the full characterization of the isolates.
Assuntos
Humanos , Animais , Adulto , Pessoa de Meia-Idade , Cães , Cobaias , Anticorpos Antivirais , Técnica Indireta de Fluorescência para Anticorpo , Vírus da Influenza A , Influenza Humana , Cavidade Nasal , Faringe , Cultura de Vírus , Argentina , Linhagem Celular , Efeito Citopatogênico Viral , Testes de Hemaglutinação , Vírus da Influenza A , Influenza Humana , Medicina do Trabalho , Estações do Ano , Sensibilidade e Especificidade , Fatores de TempoRESUMO
The maintenance of telomere length has been hypothesized to be involved in the early steps of cancerogenesis. A physiologic modulation of telomere maintenance is exerted by TRF1 (telomeric-repeat binding factor-1), which deletion permits telomere elongation. Gastrointestinal neoplastic (n=19) and non-neoplastic tissues (six inflammatory disease and six normal mucosa distant from tumor at least 5 cm) were studied, by immunohistochemistry, for TRF1 expression, by using a polyclonal antibody anti-TRF1. Differentiated and not proliferating epithelial secretory cells (Ki67 and p53 negative cells) were stained by anti-TRF1, which did not stain tumor cells in all cases but one (p<0.0001). p53 was expressed by 26% of tumor cases. Inflammatory gastrointestinal non-tumor tissues showed lower expression of TRF1 in epithelial secreting cells compared to normal tissues (p=0.008). These preliminary data suggest that down-regulation of the TRF1 expression in tumor cells may be involved in cell immortalization as an initial step in gastrointestinal carcinogenesis (before p53 alteration), and may open new perspectives, when confirmed, in gastrointestinal tumor prognosis.