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1.
  • Bjurberg, Maria, et al. (author)
  • Early changes in 2-deoxy-2-[18F]fluoro-D-glucose metabolism in squamous-cell carcinoma during chemotherapy in vivo and in vitro.
  • 2009
  • In: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 24:3, s. 327-332
  • Journal article (peer-reviewed)abstract
    • AIM: The aim of this study was to investigate early changes in uptake of 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) in vivo and in vitro in a squamous-cell carcinoma (SCC) cell line originating from a human head and neck SCC during cytotoxic therapy with respect to metabolism in tumor cells and in surrounding stromal tissue. MATERIALS AND METHODS: In 60 nude mice with xenografted SCC, 50 animals were treated with cisplatin. Early changes in the tumor FDG uptake following therapy were evaluated sequentially with phosphor imaging. Using this technique, areas with focal hypermetabolism were detected. The cells creating the focal hypermetabolism were then identified histopathologically on the corresponding sections. In addition, early FDG uptake versus the number of viable tumor cells was measured in vitro following cisplatin treatment. RESULTS: An early transient increase in FDG uptake in tumor cells was seen on day 1 in treated tumors, followed by a rapid decrease confirmed by subsequent tumor regression. This metabolic flare was present in all treated tumors but not in the controls. In vitro, an increase in FDG uptake per cell was observed. CONCLUSIONS: Our results provide new insights into the early metabolic changes in squamous-cell carcinomas subjected to cytotoxic therapy and thus contribute to the discussion on the feasibility of early predictive PET studies.
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2.
  • Brun, Eva, et al. (author)
  • Prognostic value of histopathological response to radiotherapy and microvessel density in oral squamous cell carcinomas
  • 2001
  • In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 40:4, s. 491-496
  • Journal article (peer-reviewed)abstract
    • The prognostic value of histopathological response to preoperative radiotherapy (50 Gy) in radically resected oral carcinomas was studied in 39 consecutive patients. Microvessel density (MVD) was evaluated for relation to radioresponse and outcome. Resected tumour tissue was examined histopathologically and response to radiotherapy was scored according to induced morphological changes. Pretreatment biopsies were stained with antibodies to von Willebrand factor to evaluate MVD in hot-spot regions, in stromal tissue and in tumour epithelial tissue. Histopathological response to radiotherapy was highly prognostic of local failures and survival (p = 0.002), though microscopic surgical radicality was obtained. In good responders to preoperative radiotherapy, the 5-year survival rate was 68% compared with 24% in poor responders. In 12 patients with local recurrence after radical surgery, 11 had poor histopathological radiotherapy responses. In univariate analysis, a high MVD score in tumour epithelium was associated with poor clinical outcome but MVD did not correlate with histopathological radiotherapy response.
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3.
  • Henriksson, Eva, et al. (author)
  • 2-deoxy-2-[F-18]fluoro-D-glucose uptake and correlation to intratumoral heterogeneity
  • 2007
  • In: Anticancer research. - 1791-7530. ; 27:4B, s. 2155-2159
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to investigate the pattern of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake in relation to the intratumoral histopathological appearance. Materials and Methods: Intratumoral distribution of FDG in nude mice with xenografted tumours originating from an established head and neck squamous cell carcinoma was studied. FDG uptake and the con-elation to histopathological appearance was evaluated in four separate quarters of each tumour. Results: Variations in FDG uptake correlating to the presence of tumour cells was demonstrated. Quarters containing more than 50% tumour cells showed a significantly higher FDG uptake (p=0.028) than quarters with more stromal tissue and necrosis. Conclusion: This Study shows that the heterogenic FDG uptake within a tumour correlates to histopathological findings and that the variable appearance of tracer uptake on the PET scan depends on distribution of different tissue components in the tumour. This intratumoral heterogeneity calls for caution when evaluating a PET scan where median values of larger areas will be misguiding and thus small areas with high uptake should be regarded as the regions of interest.
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4.
  • Henriksson, Eva, et al. (author)
  • Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck
  • 2009
  • In: Journal of Experimental & Clinical Cancer Research. - : Springer Science and Business Media LLC. - 1756-9966. ; 28
  • Journal article (peer-reviewed)abstract
    • Background: The survival of patients with locally advanced head and neck cancer is still poor, with 5-year survival rates of 24-35%. The identification of prognostic and predictive markers at the molecular and cellular level could make it possible to find new therapeutic targets and provide "taylor made" treatments. Established cell lines of human squamous cell carcinoma (HNSCC) are valuable models for identifying such markers. The aim of this study was to establish and characterize a series of cell lines and to compare the cisplatin sensitivity and 18F fluoro-2 deoxy 2 glucose (18F-FDG) uptake of these cell lines with other cellular characteristics, such as proliferation parameters and TP53 and CCND1 status. Methods: Explant cultures of fresh tumour tissue were cultivated, and six new permanent cell lines were established from 18 HNSCC cases. Successfully grown cell lines were analysed regarding clinical parameters, histological grade, karyotype, DNA ploidy, and index and S-phase fraction (Spf). The cell lines were further characterized with regard to their uptake of 18F-FDG, their sensitivity to cisplatin, as measured by a viability test ( crystal violet), and their TP53 and CCND1 status, by fluorescence in situ hybridization (FISH), polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) with DNA sequencing and, for cyclin D1, by immunohistochemistry. Results: Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test. Their tumours also showed more complex karyotypes than tumours from which cell lines could not be established. No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity. However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake. Conclusion: In vitro growth of HNSCC cells seem to be an independent prognostic factor, with cell lines being more readily established from aggressive tumours, a phenomenon more dependent on the molecular genetic characteristics of the tumour cells than on tumour location or TNM status.
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5.
  • Högmo, Anders, et al. (author)
  • Base of tongue squamous cell carcinomas, outcome depending on treatment strategy and p16 status. A population-based study from the Swedish Head and Neck Cancer Register
  • 2022
  • In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:4, s. 433-440
  • Journal article (peer-reviewed)abstract
    • Background: The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated.Material and methods: Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition.Results: Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively (n = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16−. 5-year overall survival (OS) was 68% (95% CI: 64–72%), with76% and 37% for p16+ patients and p16− patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II–III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone.Conclusion: In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16− tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.
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6.
  • Nyqvist, Johanna, et al. (author)
  • Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up
  • 2016
  • In: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 118:2, s. 335-341
  • Journal article (peer-reviewed)abstract
    • Background and purpose: Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer. Material and methods: 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, NO glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1 + 2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment. Results: The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline. Conclusion: In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase.
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7.
  • Abelev, Betty, et al. (author)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Journal article (peer-reviewed)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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8.
  • Abelev, Betty, et al. (author)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • In: Journal of High Energy Physics. - 1029-8479. ; :11
  • Journal article (peer-reviewed)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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9.
  • Abelev, Betty, et al. (author)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • In: Journal of High Energy Physics. - 1029-8479. ; :7
  • Journal article (peer-reviewed)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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10.
  • Adumala, Aruna, et al. (author)
  • Oral Methadone versus Morphine IR for Patients with Cervical Cancer and Neuropathic Pain : A Prospective Randomised Controlled Trial
  • 2023
  • In: Indian Journal of Palliative Care. - 0973-1075. ; 29:2, s. 200-206
  • Journal article (peer-reviewed)abstract
    • Objectives: In India, cervical cancer is the most common cancer among women and makes up for up to 29% of all registered cancer in females. Cancer-related pain is one of the major distressing symptoms for all cancer patients. Pain is characterised as somatic or neuropathic, and the total pain experience is often mixed. Conventional opioids are the backbone of analgesic treatment but are most often not sufficient in alleviating neuropathic pain, common in cervical cancer. Accumulating evidence of the advantage of methadone compared to conventional opioids, due to agonist action at both μ and δ opioid receptors, N-methyl-D-aspartate (NMDA) antagonist activity and the ability to inhibit the reuptake of monoamines has been demonstrated. We hypothesised that, with these properties’, methadone might be a good option for the treatment of neuropathic pain in patients with cervical cancer. Material and Methods: Patients with cervical cancer stages ll-lll were enrolled in this randomized controlled trial. A comparison was made between methadone versus immediate release morphine (IR morphine), with increasing doses until pain was controlled. Inclusion-period was from October 3rd to December 31st 2020, and the total patient-study period was 12 weeks. Pain intensity was assessed according to the Numeric Rating Scale (NRS) and Douleur Neuropathique (DN4). The primary objective was to determine whether methadone was clinically superior versus noninferior to morphine as an analgesic for the treatment of cancer related neuropathic pain in women with cervical cancer. Results: A total of 85 women were included; five withdrew and six died during the study period, leaving 74 patients completing the study. All participants showed a reduction in mean values of NRS and DN4 from the time of inclusion and to the end of the study period, for IR morphine and methadone 8.4–2.7 and 8.6–1.5, respectively (P < 0.001). The DN4 score mean reduction for Morphine and Methadone were 6.12–1.37 and 6.05–0, respectively (P < 0.001). Side effects were more common in the group of patients receiving IR morphine compared to the patients treated with methadone. Conclusion: We found that Methadone had a superior analgesic effect with good overall tolerability compared with morphine as a first-line strong opioid for the management of cancer-related neuropathic pain.
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