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1.
Artículo en Inglés | MEDLINE | ID: mdl-30949454

RESUMEN

Aim: This study aimed to follow the impact of human papillomavirus (HPV) catch-up and vaccination on the very high cervical HPV-prevalence in women at a youth clinic in central Stockholm during the period 2008-2018. Background: 2008-2010, cervical HPV-prevalence (69.5%) and HPV16 prevalence (34.7%) were high in non-vaccinated women at a youth clinic in Stockholm. 2013-2015, after the introduction of the quadrivalent-Gardasil® HPV-vaccine, HPV16 and HPV6 prevalence had decreased. Here, cervical HPV-prevalence was investigated 10 years after primary sampling. Material and Methods: 2017-2018, 178 cervical swabs, from women aged 15-23 years old, were tested for 27 HPV types by a bead-based multiplex method. HPV-prevalence data were then related to vaccination status and age and compared to HPV-prevalence in 615 samples from 2008 to 2010 and 338 samples from 2013 to 2015 from the same clinic, and to HPV types in 143 cervical cancer cases during 2003-2008 in Stockholm. Results: The proportion of vaccinated women increased from 10.7% (2008-2010) to 82.1% (2017-2018). The prevalence of all 27 HPVs, all high-risk HPVs (HR-HPVs) and the combined presence of the quadrivalent-Gardasil® types HPV16, 18, 6, and 11, was lower in vaccinated compared to unvaccinated women (67.4 vs. 93.3%, p = 0.0031, 60.1 vs. 86.7%, p = 0.0057 and 5.8 vs. 26.7%, p = 0.002, respectively). Furthermore, HPV16 prevalence in non-vaccinated women 2017-2018 was lower than that in 2008-2010 (16.7 and 34.7%, respectively, p = 0.0471) and similar trends were observed for HPV18 and 11. In both vaccinated and non-vaccinated women, the most common non-quadrivalent-Gardasil® vaccine HR-HPV types were HPV39, 51, 52, 56, and 59. Together they accounted for around 9.8% of cervical cancer cases in Stockholm during 2003-2008, and their prevalence tended to have increased during 2017-2018 compared to 2008-2010. Conclusion: Quadrivalent-Gardasil® vaccination has decreased HPV-vaccine type prevalence significantly. However, non-vaccine HR-HPV types remain high in potentially high-risk women at a youth clinic in Stockholm.


Asunto(s)
Cuello del Útero/virología , Vacuna Tetravalente Recombinante contra el Virus del Papiloma Humano Tipos 6, 11 , 16, 18/inmunología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Adulto , Femenino , Vacuna Tetravalente Recombinante contra el Virus del Papiloma Humano Tipos 6, 11 , 16, 18/administración & dosificación , Humanos , Epidemiología Molecular , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Prevalencia , Suecia/epidemiología , Adulto Joven
2.
Fungal Genet Biol ; 114: 42-52, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29580862

RESUMEN

In most organisms, galactose is metabolized via the Leloir pathway, which is conserved from bacteria to mammals. Utilization of galactose requires a close interplay of the metabolic enzymes, as misregulation or malfunction of individual components can lead to the accumulation of toxic intermediate compounds. For the phytopathogenic basidiomycete Ustilago maydis, galactose is toxic for wildtype strains, i.e. leads to growth repression despite the presence of favorable carbon sources as sucrose. The galactose sensitivity can be relieved by two independent modifications: (1) by disruption of Hxt1, which we identify as the major transporter for galactose, and (2) by a point mutation in the gene encoding the galactokinase Gal1, the first enzyme of the Leloir pathway. The mutation in gal1(Y67F) leads to reduced enzymatic activity of Gal1 and thus may limit the formation of putatively toxic galactose-1-phosphate. However, systematic deletions and double deletions of different genes involved in galactose metabolism point to a minor role of galactose-1-phosphate in galactose toxicity. Our results show that molecular triggers for galactose toxicity in U. maydis differ from yeast and mammals.


Asunto(s)
Galactosa/metabolismo , Ustilago/enzimología , Ustilago/genética , Secuencia de Aminoácidos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Galactoquinasa/genética , Galactoquinasa/metabolismo , Galactosafosfatos/metabolismo , Regulación Fúngica de la Expresión Génica , Genes Fúngicos/genética , Redes y Vías Metabólicas , Mutagénesis , Eliminación de Secuencia
3.
Oral Oncol ; 68: 53-59, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28438294

RESUMEN

OBJECTIVE: Head-neck cancer therapy has become intensified. With radiotherapy alone, 3-year disease-free survival (DFS) is 80% for HPV-positive TSCC/BOTSCC and better for patients with favorable characteristics, suggesting therapy could be tapered for some, decreasing side-effects. Therefore, we built a model to predict progression-free survival for patients with HPV-positive TSCC and BOTSCC. MATERIAL AND METHODS: TSCC/BOTSCC patients treated curatively between 2000 and 2011, with HPV16 DNA/E7 mRNA positive tumors examined for CD8+ TILs, HPV16 mRNA and HLA class I expression were included. Patients were split randomly 65/35 into training and validation sets, and LASSO regression was used to select a model in the training set, the performance of which was evaluated in the validation set. RESULTS: 258 patients with HPV DNA/E7 mRNA positive tumors could be included, 168 and 90 patients in the respective sets. No treatment improved prognosis compared to radiotherapy alone. CD8+ TIL counts and young age were the strongest predictors of survival, followed by T-stage <3 and presence of HPV16 E2 mRNA. The model had an area under curve (AUC) of 76%. A model where the presence of three of four of these markers defined good prognosis captured 56% of non-relapsing patients with a positive predictive value of 98% in the validation set. Furthermore, the model identified 35% of our cohort that was overtreated and could safely have received de-escalated therapy. CONCLUSION: CD8+ TIL counts, age, T-stage and E2 expression could predict progression-free survival, identifying patients eligible for randomized trials with milder treatment, potentially reducing side effects without worsening prognosis.


Asunto(s)
Biomarcadores , Carcinoma de Células Escamosas/patología , Neoplasias Orofaríngeas/patología , Infecciones por Papillomavirus/patología , Infecciones Tumorales por Virus/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/virología , Análisis de Supervivencia , Resultado del Tratamiento , Infecciones Tumorales por Virus/virología
4.
Infect Dis (Lond) ; 49(8): 588-593, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28293975

RESUMEN

BACKGROUND: The role of human papillomavirus (HPV) in tonsillar squamous cell carcinomas (TSCC) is of interest, since a considerable proportion of TSCC in Sweden and other Western countries is HPV positive. Nevertheless, the natural history of HPV in normal tonsils, and the progression from localized infection to pre-malignant lesion to cancer are poorly understood. The aim of this study was to investigate whether HPV types found in mouthwash samples correlated to those in tonsillar tissue from the same individuals undergoing tonsillectomy. METHODS: Mouthwash samples from 232 patients, aged 3-56 years, undergoing tonsillectomy, the majority with chronic tonsillitis, were collected at the time of surgery and analysed for the presence of 27 HPV types by a bead based multiplex assay. RESULTS: An HPV prevalence of 10.3% (24/232) was observed in mouthwash samples, with HPV 69 being the dominant type (10/24). Ten patients were positive for high risk HPV (HPV 16, 33, 35, 45, 56, 59). None of the tonsils resected from patients with HPV-positive mouthwash samples were positive for HPV. CONCLUSIONS: Despite an oral HPV prevalence of 10.3% in mouthwash samples from tonsillectomized patients, with dominance of HPV 69, none of the corresponding tonsillar samples exhibited the presence of HPV.


Asunto(s)
Tonsila Palatina/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Suecia/epidemiología , Tonsilectomía , Adulto Joven
5.
Anticancer Res ; 37(2): 665-673, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28179315

RESUMEN

BACKGROUND: Human papillomavirus (HPV) is a favourable prognostic factor in oropharyngeal cancer. Moreover, we and others reported that HPV-positive cancer of unknown primary in the head and neck region (HNCUP) has better outcome than HPV-negative HNCUP. However, not all studies concord. Here, our previous finding was investigated in a new cohort and additional biomarkers were analyzed. MATERIALS AND METHODS: A total of 19 HNCUPs diagnosed 2008-2013 were analyzed for HPV DNA by polymerase chain reaction assay (PCR) and p16 by immunohistochemistry (IHC). Thereafter, 69 HNCUPs diagnosed between 2000-2013 were analyzed for HPV16 mRNA by PCR (if HPV16DNA-positive) and cluster of differentiation 8 positive (CD8+) tumour-infiltrating lymphocytes (TILs) and human leukocyte antigen (HLA) class I-expression using IHC. RESULTS: HPV DNA, alone and in combination with p16 overexpression, was validated as a favourable prognostic factor in HNCUP. HPV16 mRNA was present in most HPV16 DNA-positive cases, confirming HPV-driven carcinogenesis in HNCUP. High CD8+ TIL counts indicated favourable prognosis. CONCLUSION: HPV status is useful for the management of patients with HNCUP and the role of CD8+ TILs should be further explored.


Asunto(s)
Biomarcadores de Tumor/inmunología , Linfocitos T CD8-positivos/inmunología , Neoplasias de Cabeza y Cuello/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias Primarias Desconocidas/inmunología , Infecciones por Papillomavirus/inmunología , Anciano , Inhibidor p16 de la Quinasa Dependiente de Ciclina/inmunología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , ADN Viral/genética , ADN Viral/inmunología , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/virología , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Primarias Desconocidas/diagnóstico , Neoplasias Primarias Desconocidas/virología , Papillomaviridae/genética , Papillomaviridae/inmunología , Papillomaviridae/fisiología , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Pronóstico , Sensibilidad y Especificidad
6.
Head Neck ; 39(3): 419-426, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27898186

RESUMEN

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC) has a better outcome than most head neck squamous cell carcinomas (HNSCCs) and an HPV-positive lymph node metastasis likely has an HPV-positive oropharyngeal SCC origin. Determining HPV-status in cervical lymph nodes by fine-needle aspiration cytology (FNAC) may be useful for diagnosis. METHODS: FNACs from 66 patients with neck masses were prospectively examined for HPV DNA and HPV16 mRNA by a polymerase chain reaction (PCR)-based assay, and the data correlated to diagnosis and HPV-status obtained from histopathological specimens. RESULTS: Aspirates from 17 of 66 patients, later diagnosed with HPV-positive oropharyngeal SCC, were HPV16 DNA-positive. HPV16 mRNA was detected in all cases with extractable RNA. All remaining FNACs, including 18 branchial cleft cysts, were HPV DNA-negative. HPV DNA status in the aspirates showed perfect concordance with corresponding biopsies. CONCLUSION: HPV16 DNA detection in fine-needle aspirations from neck masses is reliable and HPV16 DNA in a metastasis is a strong indicator of an HPV-positive oropharyngeal SCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 419-426, 2017.


Asunto(s)
Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Papillomavirus Humano 16/genética , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/diagnóstico , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/terapia , Estudios de Cohortes , Citodiagnóstico/métodos , ADN Viral/genética , Bases de Datos Factuales , Femenino , Papillomavirus Humano 16/aislamiento & purificación , Humanos , Inmunohistoquímica , Incidencia , Ganglios Linfáticos/patología , Ganglios Linfáticos/virología , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/epidemiología , Neoplasias Orofaríngeas/terapia , Infecciones por Papillomavirus/epidemiología , Reacción en Cadena de la Polimerasa/métodos , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , ARN Viral/genética , ARN Viral/aislamiento & purificación , Medición de Riesgo , Distribución por Sexo , Análisis de Supervivencia , Suecia
8.
Mol Clin Oncol ; 5(6): 671-674, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28105346

RESUMEN

Human papillomavirus (HPV), in addition to smoking and alcohol, is a cause of oropharyngeal squamous cell carcinoma (OPSCC), particularly of the tonsils and base of the tongue (TSCC and BOTSCC, respectively). Moreover, HPV-positive TSCC and BOTSCC are associated with a better outcome compared with their HPV-negative counterparts (80 vs. 40% 3-year disease-free survival rate, respectively) and their incidence has increased in several countries. Recently, accumulating evidence of HPV in a considerable proportion of cancers of unknown primary (CUP) in the head and neck region and in a small proportion of hypopharyngeal SCCs has been reported. Furthermore, HPV-positive tumours, particularly cases with HPV DNA positivity in combination with overexpression of p16, also tend to have a better clinical outcome compared with that of the corresponding HPV-negative tumours. This finding is particularly prominent in HPV-positive CUPs of the head and neck region, where the primary tumour likely originates from the oropharynx. Thus, the determination of HPV status and p16 expression may be of value for the diagnosis and treatment of CUP of the head and neck region and may also be of value for hypopharyngeal cancers in the future. However, for hypopharyngeal cancer as well as other non-OPSCCs, additional studies per subsite on the effect of HPV status on survival are required.

9.
Sci Adv ; 1(10): e1500947, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26665168

RESUMEN

Polar (directional) cell growth, a key cellular mechanism shared among a wide range of species, relies on targeted insertion of new material at specific locations of the plasma membrane. How these cell polarity sites are stably maintained during massive membrane insertion has remained elusive. Conventional live-cell optical microscopy fails to visualize polarity site formation in the crowded cell membrane environment because of its limited resolution. We have used advanced live-cell imaging techniques to directly observe the localization, assembly, and disassembly processes of cell polarity sites with high spatiotemporal resolution in a rapidly growing filamentous fungus, Aspergillus nidulans. We show that the membrane-associated polarity site marker TeaR is transported on microtubules along with secretory vesicles and forms a protein cluster at that point of the apical membrane where the plus end of the microtubule touches. There, a small patch of membrane is added through exocytosis, and the TeaR cluster gets quickly dispersed over the membrane. There is an incessant disassembly and reassembly of polarity sites at the growth zone, and each new polarity site locus is slightly offset from preceding ones. On the basis of our imaging results and computational modeling, we propose a transient polarity model that explains how cell polarity is stably maintained during highly active directional growth.

10.
Oral Oncol ; 51(9): 857-61, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26120094

RESUMEN

OBJECTIVES: Hypopharyngeal cancer is a subset of head neck squamous cell carcinoma (HNSCC) with particularly poor prognosis. Human papillomavirus (HPV) is a risk factor for some HNSCC, and its presence is of prognostic value for certain subsites. However, its influence on survival in hypopharyngeal cancer has not been thoroughly investigated. Here we examine HPV DNA and p16(INK4a) (p16) overexpression in relation to clinical outcome. MATERIALS AND METHODS: Hypopharyngeal tumour biopsies from 82 patients diagnosed 2008-2013 were examined for presence of HPV DNA by a bead-based multiplex assay and for p16 expression by immunohistochemistry, and the obtained data compared to that acquired previously from 109 patients diagnosed 2000-2007 at the same clinic. A survival analysis was then performed on 142 patients (from both studies) treated with curative intent and a 3-year follow-up time. RESULTS: Of the tumour biopsies 3/82 (3.7%) were HPV16 DNA and p16 positive, while 12/82 (14.6%) were p16 positive, equivalent to that in the previous study. Overall 3-year survival was significantly more favourable for patients with HPV16 DNA and p16 positive tumours as compared to survival of the other patients (86% vs. 31%, p=0.0185). A similar but not statistically significant trend was found for disease specific survival. CONCLUSION: HPV DNA and p16 positive hypopharyngeal cancer was rare and had not increased, but had a better clinical outcome as compared to other HPV-unrelated hypopharyngeal cancer. In addition, p16 overexpression was not a suitable surrogate marker for presence of HPV or for prediction of survival in this type of cancer.


Asunto(s)
Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , ADN Viral/metabolismo , Papillomavirus Humano 16/metabolismo , Neoplasias Hipofaríngeas/mortalidad , Infecciones por Papillomavirus/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Hipofaríngeas/metabolismo , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/metabolismo , Pronóstico , Análisis de Supervivencia , Suecia/epidemiología
11.
PLoS One ; 10(5): e0125937, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25955346

RESUMEN

Cell wall formation and maintenance are crucial for hyphal morphogenesis. In many filamentous fungi, chitin is one of the main structural components of the cell wall. Aspergillus nidulans ChsB, a chitin synthase, and CsmA, a chitin synthase with a myosin motor-like domain (MMD) at its N-terminus, both localize predominantly at the hyphal tip regions and at forming septa. ChsB and CsmA play crucial roles in polarized hyphal growth in A. nidulans. In this study, we investigated the mechanism by which CsmA and ChsB accumulate at the hyphal tip in living hyphae. Deletion of kinA, a gene encoding conventional kinesin (kinesin-1), impaired the localization of GFP-CsmA and GFP-ChsB at the hyphal tips. The transport frequency of GFP-CsmA and GFP-ChsB in both anterograde and retrograde direction appeared lower in the kinA-deletion strain compared to wild type, although the velocities of the movements were comparable. Co-localization of GFP-ChsB and GFP-CsmA with mRFP1-KinArigor, a KinA mutant that binds to microtubules but does not move along them, was observed in the posterior of the hyphal tip regions. KinA co-immunoprecipitated with ChsB and CsmA. Co-localization and association of CsmA with KinA did not depend on the MMD. These findings indicate that ChsB and CsmA are transported along microtubules to the subapical region by KinA.


Asunto(s)
Aspergillus nidulans/genética , Quitina Sintasa/metabolismo , Proteínas Fúngicas/genética , Hifa/genética , Cinesinas/genética , Aspergillus nidulans/crecimiento & desarrollo , Pared Celular/genética , Pared Celular/metabolismo , Quitina/metabolismo , Quitina Sintasa/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Hifa/crecimiento & desarrollo , Cinesinas/metabolismo , Mutación , Transporte de Proteínas/genética
12.
Eur J Cancer ; 51(12): 1580-7, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26025766

RESUMEN

AIM: To combine clinical and molecular markers into an algorithm for predicting outcome for individual patients with human papillomavirus (HPV) DNA/p16(INK4a) positive tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC). BACKGROUND: Head-neck cancer treatment has become more intensified, comprising not only surgery and radiotherapy, but also induction/concomitant chemotherapy and targeted therapy. With less treatment, 3-year disease free survival (DFS) is 80% for HPV-positive TSCC and BOTSCC. An 85-100% 3-year DFS is observed for HPV(+) TSCC and BOTSCC with absence of HLA class I, or CD44 expression, or high CD8(+) tumour-infiltrating lymphocyte (TIL) counts suggesting that therapy could be tapered for many if patients could be identified individually. PATIENTS AND METHODS: Patients treated curatively, with HPV DNA/p16(INK4a) positive tumours examined for HLA class I and II, CD44 and CD8(+)TILs, were included. An L1-regularised logistic regression was used to evaluate the effect of the biomarker data, age, stage, diagnosis, smoking and treatment on 3-year risk of death or relapse on a training cohort of 197 patients diagnosed 2000-2007 and validated on a cohort of 118 patients diagnosed 2008-2011. RESULTS: The variables finally included in the model were HLA class I, CD8(+) TILs, age, stage and diagnosis (TSCC or BOTSCC). The model showed acceptable discrimination and calibration. The discriminative ability of the model did not diminish after validation (AUC=0.77). CONCLUSION: To our knowledge, this is the first model to utilise information from several markers to predict an individual probability of clinical outcome for patients with HPV DNA/p16(INK4a) positive tumours.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Lengua , Neoplasias Tonsilares , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Linfocitos T CD8-positivos/inmunología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , ADN Viral/análisis , Femenino , Humanos , Receptores de Hialuranos/inmunología , Masculino , Persona de Mediana Edad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Pronóstico , Análisis de Supervivencia , Neoplasias de la Lengua/inmunología , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/virología , Neoplasias Tonsilares/inmunología , Neoplasias Tonsilares/metabolismo , Neoplasias Tonsilares/patología , Neoplasias Tonsilares/virología
13.
Transl Oncol ; 8(1): 10-7, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25749172

RESUMEN

OBJECTIVES: Patients with human papillomavirus (HPV)-positive tonsillar squamous cell carcinoma (TSCC) and base of tongue squamous cell carcinoma (BOTSCC) have a better clinical outcome than those with corresponding HPV-negative tumors. Moreover, there is a strong positive correlation between absent/low as opposed to strong HLA class I expression and favorable clinical outcome for HPV-positive tumors, while the reverse applies to HPV-negative tumors. The expression of the antigen processing machinery (APM) components TAP1, TAP2, LMP2, and LMP7 in these tumors in relation to HPV status, HLA class I expression, each other, and clinical outcome was therefore investigated. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded TSCC and BOTSCC, derived from 151 patients and previously analyzed for HPV DNA, HLA class I, and LMP10 expression were stained by immunohistochemistry for TAP1, TAP2, LMP2, and LMP7. RESULTS: Absent/low TAP2, LMP2, and LMP7 expression, similar to HLA class I and LMP10, was common in TSCC and BOTSCC, irrespective of HPV status. Expression of TAP1 and TAP2 was correlated, as was LMP2 to LMP7. LMP2 and LMP7 expression was also associated to HLA class I expression. Moreover, absence of LMP7 was linked to increased disease-free survival in both HPV-positive and HPV-negative cases. CONCLUSION: Reduced expression of TAP2, LMP2, and LMP7 was frequent in TSCC and BOTSCC and their expression as well as that of TAP1 was often interrelated. Furthermore, low LMP7 expression correlated to better clinical outcome and may, together with HPV status, potentially be used for prediction of treatment response.

14.
Viruses ; 7(3): 1332-43, 2015 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-25803099

RESUMEN

In 2007, human papillomavirus (HPV) type 16 was recognized as a risk factor by the International Agency for Research on Cancer, for oropharyngeal squamous cell carcinoma (OSCC), where tonsillar and base of tongue cancer (TSCC and BOTSCC) dominate. Furthermore, patients with HPV-positive TSCC and BOTSCC, had a much better clinical outcome than those with corresponding HPV-negative cancer and other head and neck cancer. More specifically, survival was around 80% for HPV-positive TSCC and BOTSCC vs. 40% five-year disease free survival, for the corresponding HPV-negative tumors with conventional radiotherapy and surgery, while this could not be observed for HPV-positive OSCC at other sites. In addition, the past 20-40 years in many Western Countries, the incidence of HPV-positive TSCC and BOTSCC has risen, and >70% are men. This has resulted in a relative increase of patients with HPV-positive TSCC and BOTSCC that may not need the intensified chemo-radiotherapy (with many more severe debilitating side effects) often given today to patients with head and neck cancer. However, before tapering therapy, one needs to enable selection of patients for such treatment, by identifying clinical and molecular markers that together with HPV-positive status will better predict patient prognosis and response to therapy. To conclude, there is a new increasing group of patients with HPV-positive TSCC and BOTSCC with good clinical outcome, where options for better-tailored therapy are needed. For prevention, it would be of benefit to vaccinate both girls and boys against HPV16 infection. For potential future screening the ways to do so need optimizing.


Asunto(s)
Carcinoma de Células Escamosas/epidemiología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Neoplasias de la Lengua/epidemiología , Neoplasias Tonsilares/epidemiología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virología , Humanos , Papillomaviridae/clasificación , Infecciones por Papillomavirus/mortalidad , Infecciones por Papillomavirus/terapia , Infecciones por Papillomavirus/virología , Análisis de Supervivencia , Neoplasias de la Lengua/mortalidad , Neoplasias de la Lengua/terapia , Neoplasias de la Lengua/virología , Neoplasias Tonsilares/mortalidad , Neoplasias Tonsilares/terapia , Neoplasias Tonsilares/virología , Resultado del Tratamiento
15.
Methods Mol Biol ; 1270: 347-63, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25702128

RESUMEN

Endosomes are multipurpose membranous carriers important for endocytosis and secretion. During membrane trafficking, endosomes transport lipids, proteins, and even RNAs. In highly polarized cells such as fungal hyphae, they shuttle bidirectionally along microtubules mediated by molecular motors like kinesins and dynein. For in vivo studies of these highly dynamic protein/membrane complexes, advanced fluorescence microscopy is instrumental. In this chapter, we describe live cell imaging of endosomes in two distantly related fungal model systems, the basidiomycete Ustilago maydis and the ascomycete Aspergillus nidulans. We provide insights into live cell imaging of dynamic endosomal proteins and RNA, dual-color detection for colocalization studies, as well as fluorescence recovery after photobleaching (FRAP) for quantification and photo-activated localization microscopy (PALM) for super-resolution. These methods described in two well-studied fungal model systems are applicable to a broad range of other organisms.


Asunto(s)
Endosomas/metabolismo , Hongos/metabolismo , Microscopía por Video/métodos , Imagen Molecular/métodos , Transporte Biológico , Proteínas Fúngicas/metabolismo , Procesamiento de Imagen Asistido por Computador , Unión Proteica , ARN de Hongos/metabolismo , Programas Informáticos
16.
Infect Dis (Lond) ; 47(1): 57-61, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25378085

RESUMEN

During 2009-2011, we reported that the oral and cervical prevalence of human papillomavirus (HPV) was high by international standards at 9.3% and 74%, respectively, in youth aged 15-23 years attending a youth clinic in Stockholm. After gradual introduction of public HPV vaccination during 2007-2012, between 2013 and 2014, when 73% of the women were HPV-vaccinated, but not necessarily before their sexual debut, oral HPV prevalence had dropped to 1.4% as compared with 9.3% in 2009-2011 (p < 0.00001). Cervical HPV prevalence was high and common cervical high-risk types were HPV51, 56, 59, 73, 16, 39, 52, and 53. However, it was shown that HPV16, 31, and 70 were significantly less common among HPV-vaccinated women than among those who had not received the vaccine.


Asunto(s)
Enfermedades de la Boca/epidemiología , Infecciones por Papillomavirus/epidemiología , Enfermedades del Cuello del Útero/epidemiología , Adolescente , Femenino , Estudios de Seguimiento , Humanos , Masculino , Vacunación Masiva , Enfermedades de la Boca/prevención & control , Enfermedades de la Boca/virología , Infecciones por Papillomavirus/prevención & control , Prevalencia , Suecia/epidemiología , Enfermedades del Cuello del Útero/prevención & control , Enfermedades del Cuello del Útero/virología , Adulto Joven
17.
Curr Opin Microbiol ; 20: 34-41, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24879477

RESUMEN

Cell polarization is a theme in biology conserved from bacteria to man. One of the most extremely polarized cells in nature is the hyphae of filamentous fungi. A continuous flow of secretion vesicles from the hyphal cell body to the tip is essential for cell wall and membrane extension. Microtubules (MTs) and actin, along with their corresponding motor proteins, are involved in the secretion process. Therefore, the arrangement of the cytoskeleton is a crucial step to establish and maintain polarity. Here we review recent findings unraveling the mechanism of polarized growth with special emphasis on the role of the actin and MT cytoskeletons and cell end markers linking the two cytoskeletons. We will mainly focus on Neurospora crassa and Aspergillus nidulans as model organisms.


Asunto(s)
Actinas/metabolismo , Aspergillus nidulans/crecimiento & desarrollo , Polaridad Celular , Microtúbulos/metabolismo , Neurospora crassa/crecimiento & desarrollo , Vesículas Secretoras/metabolismo , Aspergillus nidulans/metabolismo , Aspergillus nidulans/fisiología , Hifa/crecimiento & desarrollo , Hifa/metabolismo , Neurospora crassa/metabolismo , Neurospora crassa/fisiología
18.
PLoS One ; 9(4): e95624, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24752327

RESUMEN

AIM: To examine LMP10 expression and its possible impact on clinical outcome in human papillomavirus (HPV) positive and HPV-negative tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC). BACKGROUND: Outcome is better in HPV-positive TSCC and BOTSCC compared to matching HPV-negative tumours, with roughly 80% vs. 40% 5-year disease free survival (DFS) with less aggressive treatment than today's chemoradiotherapy. Since current treatment often results in harmful side effects, less intensive therapy, with sustained patient survival would be an attractive alternative. However, other markers together with HPV status are necessary to select patients and for this purpose LMP10 expression is investigated here in parallel to HPV status and clinical outcome. MATERIALS AND METHODS: From 385 patients diagnosed between 2000 and 2007 at the Karolinska University Hospital, 278 formalin fixed paraffin embedded TSCC and BOTSCC biopsies, with known HPV DNA status, were tested for LMP10 nuclear and cytoplasmic expression (fraction of positive cells and staining intensity). The data was then correlated to clinical outcome. RESULTS: An absent/low compared to a moderate/high LMP10 nuclear fraction of positive cells was correlated to a better 3-year DFS in the HPV-positive group of patients (log-rank p = 0.005), but not in the HPV-negative group. In the HPV-negative group of patients, in contrast to the HPV-positive group, moderate/high LMP10 cytoplasmic fraction and weak/moderate/high LMP10 cytoplasmic intensity correlated to a better 3-year DFS (p = 0.003 and p = 0.001) and 3-year overall survival (p = 0.001 and 0.009). CONCLUSION: LMP10 nuclear expression in the HPV-positive group and LMP10 cytoplasmic expression in the HPV-negative group of patients correlated to better clinical outcome.


Asunto(s)
Infecciones por Papillomavirus/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/virología , Neoplasias Tonsilares/metabolismo , Neoplasias Tonsilares/virología , Adulto , Anciano , Anciano de 80 o más Años , Núcleo Celular/metabolismo , Supervivencia sin Enfermedad , Femenino , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Coloración y Etiquetado , Neoplasias de la Lengua/patología , Neoplasias Tonsilares/patología , Resultado del Tratamiento
19.
Oral Oncol ; 50(5): 491-7, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24613649

RESUMEN

MATERIAL AND METHODS: Presence of HPV DNA was analyzed in mouthwash and tonsillar swab samples, if indicative of HPV-positive tonsillar or base of tongue cancer in 76 patients, with suspected head neck cancer, undergoing diagnostic endoscopy at Karolinska University Hospital. The diagnosis and tumor HPV status was later obtained from patients' records. As controls, 37 tumor-free dental visitors were included. RESULTS: Of the 76 patients, 22/29 (76%) and 16/18 (89%) had an HPV-positive tonsillar and base of tongue cancer respectively, with 18/22 (82%) and 8/16 (50%) respectively having tumor concordant HPV-type positive oral samples. Two other HPV-positive oral samples in the base of tongue cancer group did not correlate to the tumor HPV status. Among the remaining patients, 19 with other head neck cancer and 10 with benign conditions, 4/29 (14%) had HPV-positive oral samples. Consequently, of the HPV-positive oral samples, dominated by HPV16 and high signals, 27/32 (84%) were derived from 26 patients with concordant HPV-type positive tonsillar or base of tongue cancer and one patient with an unknown primary head and neck cancer. The other five HPV-positive oral samples, with mainly low signals were derived from two patients with non-concordant HPV-type positive tumor biopsies, two patients with HPV-negative tumor biopsies and a patient with a benign condition. Of the dental patients, 3/37 (8%) had HPV-positive tonsillar swabs with weak signals. CONCLUSION: In patients with suspected head neck cancer, HPV-positive oral samples, especially HPV16 with high signals, could be indicative of HPV-positive tonsillar or base of tongue cancer.


Asunto(s)
Papillomaviridae/aislamiento & purificación , Neoplasias de la Lengua/virología , Neoplasias Tonsilares/virología , Adulto , Anciano , Anciano de 80 o más Años , ADN Viral/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
20.
Eur J Contracept Reprod Health Care ; 19(2): 86-92, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24555926

RESUMEN

OBJECTIVES: To investigate sexual experiences, sexually transmitted infections (STIs) and use of condoms in relation to human papillomavirus (HPV)-vaccination status in female high school students. METHODS: In 2013, 355 female students with a median age of 18 years from randomly selected high schools in Sweden answered a classroom questionnaire on sexual experiences and HPV-vaccination status. RESULTS: In total 227/348 (65%) of the women reported having received at least one HPV vaccine dose. Median age at first intercourse was 15 and 16 years respectively, in the 141/227 (62%) vaccinated after, and the 86/227 (38%) vaccinated before their sexual debut. There were no differences between the HPV-vaccinated and non-vaccinated groups regarding condom use, STIs, and experiences of oral and anal sex, or friends- with-benefit relationships. However, having had sexual intercourse and 'one-night stands' were more common in the vaccinated group (both p < 0.05). CONCLUSION: Many students (62%) were vaccinated against HPV, with two-thirds after their sexual debut. There were no differences in condom use and STIs, and only a few differences in sexual experiences between the HPV-vaccinated and non-vaccinated groups. Initiating HPV vaccination before sexual debut is important, as is information about the link between HPV, sexual behaviour and cancer.


Asunto(s)
Condones/estadística & datos numéricos , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Conducta Sexual/estadística & datos numéricos , Enfermedades de Transmisión Sexual/prevención & control , Adolescente , Factores de Edad , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Suecia , Adulto Joven
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