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1.
J Clin Oncol ; 36(19): 1963-1972, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29746225

RESUMO

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico , Sobreviventes de Câncer/estatística & dados numéricos , Glioma/diagnóstico , Adolescente , Adulto , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/terapia , Criança , Pré-Escolar , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/terapia , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Sistema de Registros , Adulto Jovem
2.
J Neurooncol ; 132(2): 255-266, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28110411

RESUMO

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6-6.4 months) and the median overall survival is 11.0 months (95% CI 10.5-11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico por imagem , Glioma/diagnóstico por imagem , Serviços de Informação , Cooperação Internacional , Imagem por Ressonância Magnética , Sistema de Registros , Criança , Pré-Escolar , Europa (Continente) , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Ponte/diagnóstico por imagem , Adulto Jovem
3.
J Pediatr Hematol Oncol ; 34(5): 364-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22713707

RESUMO

BACKGROUND: Neonatal dried blood spots (Guthrie cards) have been used to demonstrate a prenatal origin of clonal leukemia-specific genetic aberrations in several subgroups of childhood acute lymphoblastic leukemia (ALL). One hypothesis suggests that an infectious agent could initiate genetic transformation already in utero. In search for a possible viral agent, Guthrie cards were analyzed for the presence of 3 newly discovered polyomavirus Karolinska Institutet polymavirus (KIPyV), Washington University polyomavirus (WUPyV), and Merkel cell polyomavirus (MCPyV). METHODS: Guthrie cards from 50 children who later developed ALL and 100 matched controls were collected and analyzed by standard or real-time polymerase chain reaction for the presence of the VP1 region of KIPyV, WUPyV, and MCPyV, and the LT region for MCPyV. RESULTS AND CONCLUSIONS: DNA from KIPyV, WUPyV, and MCPyV was not detected in neonatal blood samples from children with ALL or controls. Prenatal infections with these viruses are not likely to be etiological drivers for childhood leukemogenesis.


Assuntos
DNA Viral/sangue , Poliomavírus das Células de Merkel/isolamento & purificação , Polyomavirus/isolamento & purificação , Leucemia-Linfoma Linfoblástico de Células Precursoras/virologia , Adolescente , Criança , Pré-Escolar , Subunidade alfa 2 de Fator de Ligação ao Core , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia
4.
PLoS One ; 4(12): e8239, 2009 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-20011509

RESUMO

BACKGROUND: BK and JC polyomaviruses (BKV and JCV) are potentially oncogenic and have in the past inconclusively been associated with tumours of the central nervous system (CNS), while BKV has been hinted, but not confirmed to be associated with neuroblastomas. Recently three new polyomaviruses (KIPyV, WUPyV and MCPyV) were identified in humans. So far KIPyV and WUPyV have not been associated to human diseases, while MCPyV was discovered in Merkel Cell carcinomas and may have neuroepithelial cell tropism. However, all three viruses can be potentially oncogenic and this compelled us to investigate for their presence in childhood CNS and neuroblastomas. METHODOLOGY: The presence of KI, WU and MCPyV DNA was analysed, by a joint WU and KI specific PCR (covering part of VP1) and by a MCPyV specific regular and real time quantitative PCR (covering part of Large T) in 25 CNS tumour biopsies and 31 neuroblastoma biopsies from the Karolinska University Hospital, Sweden. None of the three new human polyomaviruses were found to be associated with any of the tumours, despite the presence of PCR amplifiable DNA assayed by a S14 housekeeping gene PCR. CONCLUSION: In this pilot study, the presence of MCPyV, KI and WU was not observed in childhood CNS tumours and neuroblastomas. Nonetheless, we suggest that additional data are warranted in tumours of the central and peripheral nervous systems and we do not exclude that other still not yet detected polyomaviruses could be present in these tumours.


Assuntos
Neoplasias do Sistema Nervoso Central/virologia , DNA Viral/análise , Células de Merkel/virologia , Neuroblastoma/virologia , Polyomavirus/genética , Adolescente , Anticorpos Antivirais/imunologia , Biópsia , Neoplasias do Sistema Nervoso Central/sangue , Neoplasias do Sistema Nervoso Central/patologia , Criança , DNA Viral/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neuroblastoma/patologia , Reação em Cadeia da Polimerase , Polyomavirus/imunologia , Suécia
5.
Int J Cancer ; 125(2): 362-6, 2009 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-19330833

RESUMO

In the county of Stockholm, between 1970 and 2002, we have previously reported a 3-fold parallel increase in the incidence of tonsillar squamous cell carcinoma (SCC) and the proportion of human papillomavirus (HPV) positive tonsillar SCC. Here, we have followed the above parameters in all patients (n = 120) diagnosed with tonsillar SCC during 2003-2007 in the same area, and also in correlation to our previous data. Ninety-eight pretreatment biopsies were available and presence of HPV DNA and HPV-16 E6 and E7 RNA were tested by polymerase chain reaction (PCR) and RT-PCR. Incidence data were obtained from the Swedish Cancer Registry. Data reported from 1970 to 2002 were also obtained for comparison. HPV DNA was present in 83 of 98 (85%) of the tonsillar SCC biopsies from 2003 to 2007 and 77 of these were HPV-16 positive. HPV-16 E6 and E7 RNA were found in 98% of 52 analyzed HPV-16 positive cases. The proportion of HPV-positive cancers had significantly increased both from 1970 to 2007 (p < 0.0001) as well from 2000 to 2007 (p < 0.01), with 68% (95% confidence interval (CI), 53-81) 2000-2002; 77% (95% CI, 63-87) 2003-2005; and 93% (95% CI, 82-99) 2006-2007. The incidence rate of HPV-positive tumors almost doubled each decade between 1970 and 2007, in parallel with a decline of HPV-negative tumors. In conclusion, the incidence of HPV-positive cancers is still increasing in the County of Stockholm, suggesting an epidemic of a virus-induced carcinoma, with soon practically all tonsillar SCC being HPV positive, as in cervical cancer.


Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias Tonsilares/epidemiologia , Sequência de Bases , Primers do DNA , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Prevalência , Suécia/epidemiologia , Neoplasias Tonsilares/virologia
6.
J Clin Microbiol ; 46(11): 3595-8, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18768658

RESUMO

The single most important causative factor for malignant melanomas of the skin is UV radiation. However, this is not true for melanomas on body surfaces sheltered from the sun; thus, it is important to seek new causative factors of melanoma genesis. Human papillomaviruses and gammaherpesviruses are associated with human skin cancer; for example, human papillomavirus types 5 and 8 are associated with epidermodysplasia verruciformis, and human herpesvirus 8 is associated with Kaposi's sarcoma. Recently, a newly described human polyomavirus, Merkel cell polyomavirus (MCPyV), has been associated with Merkel cell carcinoma, an unusual form of neurotropic skin cancer. Moreover, melanocytes are of neuroepithelial origin. This background impelled us to investigate if human polyomavirus DNA could play a role in the development of extracutaneous melanomas. Sixty-four extracutaneous melanomas were initially collected and dissected. Of these, 38 could be successfully used for further testing for the presence of the five human polyomaviruses known so far-BK virus (BKV), JC virus (JCV), KI polyomavirus (KIPyV), WU polyomavirus (WUPyV), and MCPyV-and of simian virus 40 (SV40). No polyomavirus DNA could be detected in any of the samples tested by use of a nested PCR detecting BKV, JCV, and SV40; a newly designed PCR detecting KIPyV and WUPyV; or a newly designed PCR for MCPyV. We conclude that since no human polyomavirus DNA was detected in primary malignant melanomas on non-sun-exposed body surfaces, these polyomaviruses presumably are not major factors for the development of extracutaneous melanomas.


Assuntos
DNA Viral/isolamento & purificação , Melanoma/virologia , Membrana Mucosa/virologia , Polyomavirus/isolamento & purificação , Humanos , Melanoma/etiologia , Reação em Cadeia da Polimerase/métodos , Polyomavirus/genética
7.
Anticancer Res ; 26(2B): 1311-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16619539

RESUMO

The significance of the BK virus (BKV) and possible co-factors for the development of late onset haemorrhagic cystitis (HC) in allogeneic haematopoetic stem cell (HSCT)-transplanted patients is reviewed. BKV-associated HC causes significant morbidity and mortality in HSCT patients, however, BK-viruria cannot distinguish patients at risk of HC, since it is observed in patients with and without HC. Several studies have therefore attempted to identify co-factors for the development of HC. Acute graft versus host disease was in the past, though less so recently, reported to correlate to the incidence of HC. However, patients who had received grafts from unrelated donors (URD) and had had full conditioning prior to HSCT were shown to have an increased risk of HC, compared to patients who had received HSCT from a related donor (RD) or patients who had received reduced intensity conditioning. In conclusion, HSCT patients with BK-viruria, an URD and receiving full conditioning have an increased risk of developing HC.


Assuntos
Vírus BK/fisiologia , Cistite/etiologia , Cistite/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Vírus BK/genética , Cistite/genética , Cistite/virologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/virologia , Humanos , Infecções por Polyomavirus/etiologia , Infecções por Polyomavirus/genética , Infecções por Polyomavirus/prevenção & controle , Infecções por Polyomavirus/virologia , Doadores de Tecidos , Transplante Homólogo , Infecções Tumorais por Vírus/etiologia , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/prevenção & controle , Infecções Tumorais por Vírus/virologia
8.
Haematologica ; 91(3): 401-4, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16531266

RESUMO

The influence of BK-viruria, donor background, and conditioning on the development of hemorrhagic cystitis was examined in 90 allogeneic hematopoetic stem cell transplant patients, of whom 15 developed hemorrhagic cystitis. Thirty-two patients had related and 58 had unrelated donors, while 44 received full, and 46 received reduced intensity conditioning (RIC). BK-viruria was more common in patients with hemorrhagic cystitis than in those without (p<0.01), and hemorrhagic cystitis was less common in patients with related donors than in those with unrelated donors (p=0.02). Finally, hemorrhagic cystitis and BK-viruria were less common in patients receiving RIC, rather than full conditioning (p<0.01 and p<0.01, respectively).


Assuntos
Vírus BK , Cistite/epidemiologia , Cistite/virologia , Transplante de Células-Tronco Hematopoéticas , Hemorragia/epidemiologia , Hemorragia/virologia , Infecções por Polyomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Urina/virologia , Adolescente , Adulto , Criança , Cistite/urina , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/urina , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/cirurgia , Infecções por Polyomavirus/urina , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Infecções Tumorais por Vírus/cirurgia , Infecções Tumorais por Vírus/urina
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