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  • 1.
    Alizadeh, Javad
    et al.
    University of Manitoba, Canada.
    Zeki, Amir A.
    Centre Comparat Resp Biol and Med, CA USA.
    Mirzaei, Nima
    University of Manitoba, Canada.
    Tewary, Sandipan
    University of Manitoba, Canada.
    Rezaei Moghadam, Adel
    University of Manitoba, Canada; University of Manitoba, Canada.
    Glogowska, Aleksandra
    University of Manitoba, Canada.
    Nagakannan, Pandian
    University of Manitoba, Canada.
    Eftekharpour, Eftekhar
    University of Manitoba, Canada.
    Wiechec, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Gordon, Joseph W.
    University of Manitoba, Canada; University of Manitoba, Canada; University of Manitoba, Canada.
    Xu, Fred. Y.
    University of Manitoba, Canada; University of Manitoba, Canada.
    Field, Jared T.
    University of Manitoba, Canada.
    Yoneda, Ken Y.
    Centre Comparat Resp Biol and Med, CA USA.
    Kenyon, Nicholas J.
    Centre Comparat Resp Biol and Med, CA USA.
    Hashemi, Mohammad
    Zehedan University of Medical Science, Iran.
    Hatch, Grant M.
    University of Manitoba, Canada; University of Manitoba, Canada.
    Hombach-Klonisch, Sabine
    University of Manitoba, Canada.
    Klonisch, Thomas
    University of Manitoba, Canada.
    Ghavami, Saeid
    University of Manitoba, Canada; University of Manitoba, Canada; Shiraz University of Medical Science, Iran.
    Mevalonate Cascade Inhibition by Simvastatin Induces the Intrinsic Apoptosis Pathway via Depletion of Isoprenoids in Tumor Cells2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 44841Article in journal (Refereed)
    Abstract [en]

    The mevalonate (MEV) cascade is responsible for cholesterol biosynthesis and the formation of the intermediate metabolites geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) used in the prenylation of proteins. Here we show that the MEV cascade inhibitor simvastatin induced significant cell death in a wide range of human tumor cell lines, including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, and breast cancer. Simvastatin induced apoptotic cell death via the intrinsic apoptotic pathway. In all cancer cell types tested, simvastatin-induced cell death was not rescued by cholesterol, but was dependent on GGPP-and FPP-depletion. We confirmed that simvastatin caused the translocation of the small Rho GTPases RhoA, Cdc42, and Rac1/2/3 from cell membranes to the cytosol in U251 (glioblastoma), A549 (lung adenocarcinoma) and MDA-MB231( breast cancer). Simvastatin-induced Rho-GTP loading significantly increased in U251 cells which were reversed with MEV, FPP, GGPP. In contrast, simvastatin did not change Rho-GTP loading in A549 and MDA-MB-231. Inhibition of geranylgeranyltransferase I by GGTi-298, but not farnesyltransferase by FTi-277, induced significant cell death in U251, A549, and MDA-MB-231. These results indicate that MEV cascade inhibition by simvastatin induced the intrinsic apoptosis pathway via inhibition of Rho family prenylation and depletion of GGPP, in a variety of different human cancer cell lines.

  • 2.
    Axelsson, Hanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology.
    Björkegren, Joline
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology.
    Personer som har traumatisk hjärnskada: Upplevelser av skadan och kommunikation efter skadan2017Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    An alteration in the function of the brain caused by an external force is called a Traumatic Brain Injury (TBI). There are language features located in different areas of the brain, and depending on where a person gets a TBI, the person can experience different communicative difficulties. These can manifest as aphasia, dysarthria or cognitive communicative disorders. The experiences of TBI that have been discovered in previous studies are for instance about how persons with TBI experience their diminished functions, life adjustment after the injury, the role and support of the relatives, that the environment treats them differently after the injury and emotional consequences. For the purpose of investigation and intervention, ICF is a useful tool since the difficulties that a person may have can be connected to its various components.

    The purpose of this study is to examine what experiences persons with TBI have regarding their brain injury and their communicative difficulties, and also how these can be connected to ICF. To answer the research questions, a qualitative method involving content analysis was used, based on semi-structured interviews with four participants.

    The participants expressed that their TBI had affected them in various ways, communicative, cognitive, physically and socially. The participants experienced their injuries and difficulties as limiting and that some periods had been lonely. However they also stated that there were some positive aspects in the situation, for example improved family relations and that they valued life in another way.

    Although the injuries, difficulties and rehabilitation of the participants have differed, the participants stories have been similar to some extent. In the future it would be interesting to conduct further studies in Sweden that examine which experiences persons with TBI have regarding the injury itself, but particularly regarding their communication after the TBI. It is important with more studies since that would give speech language pathologists a greater understanding for how people with TBI experience their situation and their communication after the injury. 

  • 3.
    Hengen, Johanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Peterson, Malin
    Specialpedagogiskt Centre, Sweden.
    McAllister, Anita
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Patient characteristics and intervention effect as measured by Voice Handicap Index2017In: Logopedics, Phoniatrics, Vocology, ISSN 1401-5439, E-ISSN 1651-2022, Vol. 42, no 2, 93-98 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To analyze patients with a confirmed voice disorder in order to identify patterns regarding age, gender, and occupation compared to the general public. To explore effects of voice therapy according to the Voice Handicap Index (VHI) score pre- and post-therapy in relation to the number of sessions, age, and gender. Design: Prospective cohort study. Materials and methods: This study was conducted as a collaborative project between Linkoping University and hospitals in the south-east health care region in Sweden. Six voice clinics participated by asking their patients voluntarily to complete the Swedish version of the VHI at the beginning and end of therapy. Results and conclusions: The two most prevalent diagnoses were dysphonia (43%) and phonasthenia (25%). Among the working population, the three most common occupational fields were education, health care, and child-care. The majority of the patients were women (74.3%), and the mean age of all patients was 55 years. A significant improvement in VHI scores was found after therapy, with an average decrease of 19 median points in total score and a substantial effect size (0.55). The number of sessions did not significantly correlate with the mean VHI score difference but had a weak correlation to the start and end scores. Increasing age correlated with a higher median VHI score both at the start and end of therapy but did not affect the average decrease between the two measurements.

  • 4.
    Karlsson, Kajsa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology.
    Thormeyer, Ida
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology.
    Språkliga förmågor i relation till läsförmåga hos ungdomar och unga vuxna med lindrig intellektuell funktionsnedsättning2017Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Previous studies have shown that individuals exhibiting mild intellectual disability show a lower reading ability than individuals with typical development. The reasons behind these differences are unclear. However, research shows that specific language abilities affect reading ability. The present study aims to investigate any possible correlations between language ability and reading ability in young people with mild intellectual disability, aged 12 to 25 years. The examined linguistic abilities were phonological awareness, rapid automatized naming (RAN), vocabulary, grammatical comprehension and language comprehension. Testing was held at the participants’ schools in various parts of central and southern Sweden. The raw scores were used in correlation and regression analyses to map out any correlations.

    A total of 27 participants with ages ranging between 13;06 years and 25;09 years were included in the study. The results showed that RAN and phonological awareness had strong significant correlations to decoding and that they together can account for 72.3 % of its variance. Reading comprehension showed strong significant correlations to phonological awareness, grammatical comprehension, decoding, and language comprehension. Language comprehension and vocabulary explained 62.4 % of the variance in reading comprehension. Word decoding showed a stronger correlation to reading comprehension than phonological decoding.

    The results of the present study are in large parts compatible with previous research, which supports the findings that phonological awareness and RAN are of importance to decoding ability, and that decoding in turn has an impact on reading comprehension in individuals with both typical development and intellectual disability. However, the results in the present study are at odds with previous research, which has not found significant correlations between vocabulary and reading comprehension in individuals with mild intellectual disability.

    In summation, results of the present study show that a number of linguistic abilities can explain the variance of both decoding and reading comprehension. Hopes are that the results from the present study can contribute to furthering knowledge of the underlying factors which explain why individuals with mild intellectual disabilities generally are poor readers. More research is needed to confirm which other factors can explain the remaining variance and to strengthen the results of the present study.

  • 5.
    Kim, Jeewon
    et al.
    Stanford University, CA 94305 USA.
    Ho Shin, June
    Stanford University, CA 94305 USA.
    Chen, Che-Hong
    Stanford University, CA 94305 USA.
    Cruz, Leslie
    Stanford University, CA 94305 USA.
    Farnebo, Lovisa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping. Stanford University, CA 94305 USA.
    Yang, Jieying
    Stanford University, CA 94305 USA.
    Borges, Paula
    Stanford University, CA 94305 USA.
    Kang, Gugene
    Stanford University, CA 94305 USA.
    Mochly-Rosen, Daria
    Stanford University, CA 94305 USA.
    Sunwoo, John B.
    Stanford University, CA 94305 USA; Stanford University, CA 94305 USA.
    Targeting aldehyde dehydrogenase activity in head and neck squamous cell carcinoma with a novel small molecule inhibitor2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 32, 52345-52356 p.Article in journal (Refereed)
    Abstract [en]

    Chemoresistant cancer cells express high levels of aldehyde dehydrogenases (ALDHs), particularly in head and neck squamous cell carcinoma (HNSCC). The ALDH family of enzymes detoxify both exogenous and endogenous aldehydes. Since many chemotherapeutic agents, such as cisplatin, result in the generation of cytotoxic aldehydes and oxidative stress, we hypothesized that cells expressing high levels of ALDH may be more chemoresistant due to their increased detoxifying capacity and that inhibitors of ALDHs may sensitize them to these drugs. Here, we show that overall ALDH activity is increased with cisplatin treatment of HNSCC and that ALDH3A1 protein expression is particularly enriched in cells treated with cisplatin. Activation of ALDH3A1 by a small molecule activator (Alda-89) increased survival of HNSCC cells treated with cisplatin. Conversely, treatment with a novel small molecule ALDH inhibitor (Aldi-6) resulted in a marked decrease in cell viability, and the combination of Aldi-6 and cisplatin resulted in a more pronounced reduction of cell viability and a greater reduction in tumor burden in vivo than what was observed with cisplatin alone. These data indicate that ALDH3A1 contributes to cisplatin resistance in HNSCC and that the targeting of ALDH, specifically, ALDH3A1, appears to be a promising strategy in this disease.

  • 6.
    Lindblad, Carolina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology.
    Löfström, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology.
    Påverkan på tal- och språkproduktion vid transkraniell magnetstimulering, TMS, hos personer med hjärntumör2017Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    When an individual is diagnosed with a brain tumour, intervention by neurosurgery might be needed. In case of neurosurgery, a preoperative assessment of the individual’s language functions is carried out, if possible, in order to identify sensitive language areas in cortical structures. Today, nTMS, navigated transcranial magnetic stimulation, is being used, which temporarily shuts down functions in specific cortical areas and thus is a useful method to fulfill this aim. The patient is asked to name a series of pictures representing nouns while focal parts of the brain is stimulated with magnetic stimulation.

    The purpose of the present study was to examine whether the naming ability of nouns changed during nTMS in individuals with brain tumour and in what way, as well as whether the location of the tumour affected the participants naming abilities during nTMS.

    All participants in the present study were patients with brain tumour, previously examined with nTMS in a neurophysiological clinic at a hospital in the South East of Sweden. The examinations were video recorded and have subsequently formed the material for data analysis in the present study. Analysis was made on group and population level. The groups were created based on the participants tumour localisation.

    The result shows that the naming ability changes as a number of language related phenomenon aroused in the preoperative examination using nTMS. The five most common phenomena on population level were hesitation sound, latency, sound interjection, no response and inaccurate articulation. Comparison on group level revealed no significant difference regarding tumour location.

    The result might indicate that the neurophysiology of language consists of collaborating complex networks. The result can also support theories regarding tumour induced plasticity.

  • 7.
    Lohmander, Anette
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Hagberg, Emilie
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Persson, Christina
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Willadsen, Elisabeth
    University of Copenhagen, Denmark.
    Lundeborg Hammarström, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Davies, Julie
    Royal Manchester Childrens Hospital, England.
    Havstam, Christina
    Sahlgrens University Hospital, Sweden.
    Boers, Maria
    University Hospital Copenhagen, Denmark.
    Kisling-Moller, Mia
    Cleft Palate Centre, Denmark.
    Alaluusua, Suvi
    University of Helsinki, Finland.
    Aukner, Ragnhild
    Statped Sorost, Norway.
    Helen Pedersen, Nina
    Statped Vest, Norway.
    Turunen, Leena
    University of Helsinki, Finland.
    Nyberg, Jill
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Validity of auditory perceptual assessment of velopharyngeal function and dysfunction - the VPC-Sum and the VPC-Rate2017In: Clinical Linguistics & Phonetics, ISSN 0269-9206, E-ISSN 1464-5076, Vol. 31, no 7-9, 589-597 p.Article in journal (Refereed)
    Abstract [en]

    Overall weighted or composite variables for perceptual auditory estimation of velopharyngeal closure or competence have been used in several studies for evaluation of velopharyngeal function during speech. The aim of the present study was to investigate the validity of a composite score (VPC-Sum) and of auditory perceptual ratings of velopharyngeal competence (VPC-Rate). Available VPC-Sum scores and judgments of associated variables (hypernasality, audible nasal air leakage, weak pressure consonants, and non-oral articulation) from 391 5-year olds with repaired cleft palate (the Scandcleft project) were used to investigate content validity, and 339 of these were compared with an overall judgment of velopharyngeal competence (VPC-Rate) on the same patients by the same listeners. Significant positive correlations were found between the VPC-Sum and each of the associated variables (Cronbachs alpha 0.55-0.87, P amp;lt; 0.001), and a moderately significant positive correlation between VPC-Sum and VPC-Rate (Rho 0.698, P amp;lt; 0.01). The latter classified cases well when VPC-Sum was dichotomized with 67% predicted velopharyngeal competence and 90% velopharyngeal incompetence. The validity of the VPC-Sum was good and the VPC-Rate a good predictor, suggesting possible use of both measures depending on the objective.

  • 8.
    Ruhi Soylu, Abdullah
    et al.
    Hacettepe University, Turkey.
    Yavas, Gorkem
    Hacettepe University, Turkey.
    Ergin, Bora
    Hacettepe University, Turkey.
    Keceli, Sumru
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Effect of touch coordinate display as a form of augmented, concurrent visual feedback on the accuracy of single-handed typing via smartphone virtual keyboards2017In: Turkish Journal of Electrical Engineering and Computer Sciences, ISSN 1300-0632, E-ISSN 1303-6203, Vol. 25, no 3, 1724-1732 p.Article in journal (Refereed)
    Abstract [en]

    This study assessed the effect of an easily perceived real-time visual feedback method on touchscreen typing accuracy. Thirty subjects were asked to hold a smartphone with a capacitive touchscreen in one hand and enter a text using the thumb of the same hand via a custom designed virtual keyboard. There were two types of text entry sessions: with or without visual feedback. The visual feedback consisted of a full-screen crosshair, representing the accurate coordinate of touch in real time. In each session, touch-down time on the virtual keyboard and touch coordinates were recorded for every touch action. Two types of typing errors were defined: 1) centering error (CE), which was calculated as the mm distance between the coordinate of the touch and the center of the key, and 2) incorrect entry (IE), which was the number of missed keys. Student t-tests and Wilcoxon tests were used for mean and mean-rank comparisons of CE and IE, respectively. The results showed that visual feedback decreased CE (mean SD) significantly from 1.34 +/- 0.38 mm to 0.85 +/- 0.24 mm (P amp;lt; 0.0005), and decreased IE (median and range, # of incorrect entries) significantly from 5.50 and 32.00 to 1.00 and 7.00 (P amp;lt; 0.005). In conclusion, the accurate, easily perceived, and 2D real-time feedback decreases touch-typing error rates markedly and therefore can be of practical importance for increasing the productivity of smartphone users.

  • 9.
    Samuelsson, Christina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Hydén, Lars-Christer
    Linköping University, Department of Social and Welfare Studies, NISAL - National Institute for the Study of Ageing and Later Life. Linköping University, Faculty of Arts and Sciences.
    Collaboration, trouble and repair in multiparty interactions involving couples with dementia or aphasia2017In: International Journal of Speech-Language Pathology, ISSN 1754-9507, E-ISSN 1754-9515, Vol. 19, no 5, 454-464 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of the present study was to identify problems with communication with persons with aphasia and persons with dementia in a collaborative interview setting with their significant others. In particular, to compare interactional practices used in order to resolve problems caused by specific symptoms. Method: Five persons with aphasia and five persons with dementia and their spouses participated in the study. Interviews were carried out couple by couple, and the interviews had a task-oriented character. The interviews were video and audio recorded. All interviews were transcribed. From the transcriptions categorisations according to previous literature were made. Result: The results demonstrated that repair sequences were frequent in interaction involving people with aphasia (PWA), and even more so in interaction involving persons with dementia (PWD). In general, it was the PWA/PWD that initiated the repair sequence more often than the spouse, thus keeping the general rule of a preference for self-initiated repair compared to other-initiated repair. Conclusion: The active involvement of the conversational partners in trouble solving sequences in interaction with PWA/PWD demonstrated in the present study indicates that the interactional style of the conversational partner to PWA/PWD important. This implies that conversation partner training programmes would be useful both for PWA and for PWD.

  • 10.
    Skonieczna, Magdalena
    et al.
    Silesian University of Technology.
    Cieslar-Pobuda, Artur
    Centre for Molecular Medicine, Norway .
    Saenko, Yuriy
    S.P.Kapitsa Technological Research Institute.
    Foksinski, Marek
    Collegium Medicum in Bydgoszcz, Poland.
    Olinski, Ryszard
    Collegium Medicum in Bydgoszcz, Poland.
    Rzeszowska-Wolny, Joanna
    Silesian University of Technology, Poland.
    Wiechec, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    The impact of DIDS-induced inhibition of voltage-dependent anion channels (VDAC) on cellular response of lymphoblastoid cells to ionizing radiation.2017In: Medicinal chemistry, ISSN 1573-4064, Vol. 13, no 5, 477-483 p.Article in journal (Refereed)
    Abstract [en]

    Background: The voltage-dependent ion channels (VDAC) play an essential role in the cross talk between mitochondria and the rest of the cell. Their implication in cell life and cell death has been studied extensively in recent years. In this work we studied the impact of mitochondrial membrane voltage-dependent anion channels (VDACs) on cell survival and response to X-ionizing radiation (IR) of human lymphoblastoid K562 cells. Methods: The inhibition of VDACs was achieved by 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) inhibitor and in vitro experiments including clonogenity assay, UV-visible spectrophotometry, comet assay and FACS analysis were implemented. Results: Inhibition of VDAC led to augmentation of IR-induced apoptosis and ROS production. Additionally, DIDS affected repair of IR-induced DNA strand breaks and was in line with both induction of apoptosis and caspase activity. The IR-induced NO production was potently reduced by inhibition of VDAC. Conclusion: Our results suggest that VDAC control cellular response to ionizing radiation through modulation of the ROS- and NO-dependent signaling pathways. Inhibition of VDAC with DIDS induced apoptosis in irradiated K562 lymphoblastoid cells points at DIDS, as a promising agent to enhance the effectiveness of radiotherapy.

    The full text will be freely available from 2018-06-01 16:32
  • 11.
    Tiefenböck Hansson, Katharina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Haapaniemi, Aaro
    Helsinki University Hospital, Finland; University of Helsinki, Finland.
    Farnebo, Lovisa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Palmgren, Bjorn
    Karolinska University Hospital, Sweden.
    Tarkkanen, Jussi
    University of Helsinki, Finland; Helsinki University Hospital, Finland.
    Farnebo, Marianne
    Karolinska Institute, Sweden.
    Munck-Wikland, Eva
    Karolinska University Hospital, Sweden.
    Makitie, Antti
    Helsinki University Hospital, Finland; University of Helsinki, Finland; Karolinska University Hospital, Sweden.
    Garvin, Stina
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    WRAP53 beta, survivin and p16(INK4a) expression as potential predictors of radiotherapy/chemoradiotherapy response in T2N0-T3N0 glottic laryngeal cancer2017In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 38, no 4, 2062-2068 p.Article in journal (Refereed)
    Abstract [en]

    The current treatment recommendation for T2-3N0M0 glottic squamous cell carcinoma (SCC) in the Nordic countries comprises of radiotherapy (RT) and chemoradiotherapy (CRT). Tumor radiosensitivity varies and another option is primary surgical treatment, which underlines the need for predictive markers in this patient population. The aim of the present study was to investigate the relation of the proteins WRAP53 beta, survivin and p16INK4a to RT/CRT response and ultimate outcome of patients with T2-T3N0 glottic SCC. Protein expression was determined using immunohistochemistry on tumors from 149 patients consecutively treated with RT or CRT at Helsinki University Hospital, Karolinska University Hospital, and Linkping University Hospital during 1999-2010. Our results demonstrate a significantly better 5-year relapse-free survival, disease-free survival (DFS), disease-specific survival and overall survival of patients with T3N0 tumors treated with CRT compared with RT alone. Patients with tumors showing a cytoplasmic staining of WRAP53 beta revealed significantly worse DFS compared with those with nuclear staining. For survivin, we observed a trend towards better 5-year DFS in patients with strong nuclear survivin expression compared with those with weak nuclear survivin expression (p=0.091). Eleven (7%) tumors showed p16 positivity, with predilection to younger patients, and this age group of patients with p16-positive SCC had a significantly better DFS compared with patients with p16-negative SCC. Taken together, our results highlight WRAP53 beta as a potential biomarker for predicting RT/CRT response in T2-T3N0 glottic SCC. p16 may identify a small but distinct group of glottic SCC with favorable outcome. Furthermore, for T3N0 patients better outcome was observed following CRT compared to RT alone.

  • 12.
    Willadsen, Elisabeth
    et al.
    University of Copenhagen, Denmark.
    Lohmander, Anette
    Karolinska University Hospital, Sweden.
    Persson, Christina
    Sahlgrens University Hospital, Sweden; University of Gothenburg, Sweden.
    Lundeborg, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Alaluusua, Suvi
    University of Helsinki, Finland.
    Aukner, Ragnhild
    Statped Sorost, Norway.
    Bau, Anja
    University of Copenhagen Hospital, Denmark.
    Boers, Maria
    University of Copenhagen Hospital, Denmark.
    Bowden, Melanie
    Royal Manchester Childrens Hospital, England.
    Davies, Julie
    Royal Manchester Childrens Hospital, England.
    Emborg, Berit
    Cleft Palate Centre, Denmark.
    Havstam, Christina
    Sahlgrens University Hospital, Sweden.
    Hayden, Christine
    Royal Hospital Sick Children, North Ireland.
    Henningsson, Gunilla
    Karolinska University Hospital, Sweden.
    Holmefjord, Anders
    Statped Vest, Norway.
    Hölttä, Elina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences.
    Kisling-Moller, Mia
    Cleft Palate Centre, Denmark.
    Kjoll, Lillian
    Statped Sorost, Norway.
    Lundberg, Maria
    Karolinska University Hospital, Sweden.
    McAleer, Eilish
    Royal Hospital Sick Children, North Ireland.
    Nyberg, Jill
    Karolinska University Hospital, Sweden.
    Paaso, Marjukka
    University of Helsinki, Finland.
    Helen Pedersen, Nina
    Statped Vest, Norway.
    Rasmussen, Therese
    Statped Vest, Norway.
    Reisaeter, Sigvor
    Statped Vest, Norway.
    Sogaard Andersen, Helene
    University of Copenhagen Hospital, Denmark.
    Schops, Antje
    University of Copenhagen Hospital, Denmark.
    Tordal, Inger-Beate
    Statped Sorost, Norway.
    Semb, Gunvor
    Statped Sorost, Norway; University of Manchester, England; National Hospital Norway, Norway.
    Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate: 5. Speech outcomes in 5-year-olds - consonant proficiency and errors2017In: Journal of Plastic Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 51, no 1, 38-51 p.Article in journal (Refereed)
    Abstract [en]

    Background and aim: Normal articulation before school start is a main objective in cleft palate treatment. The aim was to investigate if differences exist in consonant proficiency at age 5 years between children with unilateral cleft lip and palate (UCLP) randomised to different surgical protocols for primary palatal repair. A secondary aim was to estimate burden of care in terms of received additional secondary surgeries and speech therapy. Design: Three parallel group, randomised clinical trials were undertaken as an international multicentre study by 10 cleft teams in five countries: Denmark, Finland, Norway, Sweden, and the UK. Methods: Three different surgical protocols for primary palatal repair were tested against a common procedure in the total cohort of 448 children born with non-syndromic UCLP. Speech audio- and video-recordings of 391 children (136 girls and 255 boys) were available and transcribed phonetically. The main outcome measure was Percent Consonants Correct (PCC) from blinded assessments. Results: In Trial 1, arm A showed statistically significant higher PCC scores (82%) than arm B (78%) (p=.045). No significant differences were found between prevalences in Trial 2, A: 79%, C: 82%; or Trial 3, A: 80%, D: 85%. Across all trials, girls achieved better PCC scores, excluding s-errors, than boys (91.0% and 87.5%, respectively) (p=.01). Conclusions: PCC scores were higher in arm A than B in Trial 1, whereas no differences were found between arms in Trials 2 or 3. The burden of care in terms of secondary pharyngeal surgeries, number of fistulae, and speech therapy visits differed.

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