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- Tallini, G, et al.
(författare)
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Correlation between clinicopathological features and karyotype in 100 cartilaginous and chordoid tumours. A report from the Chromosomes and Morphology (CHAMP) Collaborative Study Group
- 2002
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417. ; 196:2, s. 194-203
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Tidskriftsartikel (refereegranskat)abstract
- The evaluation of chondroid lesions requires full integration of clinical, radiographic, and pathological data; tumour typing is often a challenge for the diagnostic pathologist. Although a variety of chromosomal abnormalities have been documented in chondroid lesions, the potential usefulness of cytogenetic analysis remains unclear. This study has critically reviewed and analysed 117 karyotyped samples from 100 patients with cartilaginous and chordoid tumours. Cases were selected based on successful chromosomal analysis and adequacy of clinical, radiographic, and pathological information. To ensure objective evaluation, the cytogenetic results were correlated in a double-blind setting with consensus diagnoses independently determined on each case, after complete review of the histological, radiographic, and clinical findings. Karyotypic aberrations were identified in 41/92 cartilaginous tumours (5/11 osteochondromas, 2/3 chondromyxoid fibromas, 0/4 chondroblastomas, 11/29 chondromas, 0/3 chondroid tumours of undetermined malignant potential, 22/40 chondrosarcomas and 1/2 miscellaneous cartilaginous lesions) and 5/8 chordomas. Complex karyotypic changes were a feature of malignant tumours (chondrosarcoma and chordoma) and of chondrosarcoma among cartilaginous tumours, where they correlated with high tumour grade. Among primary well-differentiated cartilaginous lesions of bone, the finding of an abnormal karyotype was consistently associated with a grade 1 chondrosarcoma diagnosis. Among karyotypically abnormal cartilaginous tumours, loss of distal 8q was associated with osteochondroma, +5 with synovial chondroma/chondromatosis and parosteal or soft tissue chondroma, alterations of chromosome arm 6q with chondromyxoid fibroma, +7 with bone chondrosarcoma, and 17pl alterations with grade 3 chondrosarcoma. Alterations involving 12q13 characterized synovial chondroma/chondromatosis in the chondroma group and myxoid chondrosarcoma of bone in the chondrosarcoma group. In conclusion, cytogenetic abnormalities in chondroid lesions are common and are not randomly distributed. They are associated with malignancy/tumour grade as well as with specific diagnoses in many cases, and can therefore be of potential value for tumour typing.
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| 2. |
- Mertens, F, et al.
(författare)
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Cytogenetic findings in 33 osteosarcomas
- 1993
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 55:1, s. 44-50
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-three osteosarcomas (OS) were analyzed cytogenetically. Clonal chromosome changes were detected in 17 cases. Six tumors had chromosome numbers in the diploid range, 6 in the triploid range, 1 in the tetraploid range and 1 in the pentaploid range, while 3 tumors had multiple clones with different ploidy levels. Including the present 17 tumors, a total of 27 OS with clonal aberrations have been reported. The recognizable structural rearrangements in these 27 tumors clustered to chromosome arms 1p, 1q, 3p, 3q, 7q, 11p, 17p and 22q. Chromosome bands 1q11, 1q21, 1q42 and 7q11 were the most frequently rearranged, and the most common numerical rearrangements were -3, -10, -13 and -15. Supernumerary ring chromosomes, in 2 tumors as the sole change, were found in all 3 parosteal OS, which is in agreement with the findings in 1 previously reported parosteal OS. The association between ring formation and parosteal morphology represents the first cytogenetic-morphologic entity among OS.
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| 3. |
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| 4. |
- Rydholm, H., et al.
(författare)
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Reducing Adverse Effects During Drug Development: The Example of Lesogaberan and Paresthesia
- 2016
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Ingår i: Clinical Therapeutics. - : Elsevier BV. - 0149-2918. ; 38:4, s. 946-960
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Lesogaberan, a gamma-aminobutyric acid (GABA)(B) receptor agonist, was developed for the treatment of gastroesophageal reflux disease in patients with a partial response to proton pump inhibitor therapy. A high prevalence of paresthesia was observed in healthy individuals after dosing with lesogaberan in early-phase clinical trials. The aim of this review was to gain further insight into paresthesia caused by lesogaberan by summarizing the relevant preclinical and clinical data. Methods: This study was a narrative review of the literature and unpublished data. Findings: The occurrence of paresthesia may depend on the route or rate of drug administration; several studies were conducted to test this hypothesis, and formulations were developed to minimize the occurrence of paresthesia. Phase I clinical studies showed that, in healthy individuals, paresthesia occurred soon after administration of lesogaberan in a dose-dependent manner regardless of the route of administration. The occurrence of paresthesia could be decreased by fractionating the dose or reducing the rate of administration. These findings suggest that the initial rate of absorption plays an important part in the development of paresthesia. Modified-release formulations minimize the occurrence of paresthesia while retaining the anti-reflux activity of the drug, as measured by esophageal pH and the number of transient lower esophageal sphincter relaxations. Implications: The development of lesogaberan was halted because the effect on gastroesophageal reflux disease symptoms observed in Phase II studies was not considered clinically meaningful in the target patient population. Nevertheless, it is an example of successful formulation development designed to minimize the occurrence of a compound's adverse effect while retaining its pharmacodynamic action. (C) 2016 Elsevier HS Journals, Inc. All rights reserved.
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| 9. |
- Choong, P F, et al.
(författare)
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Prognostic value of Ki-67 expression in 182 soft tissue sarcomas. Proliferation--a marker of metastasis?
- 1994
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - 1600-0463. ; 102:12, s. 915-924
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Tidskriftsartikel (refereegranskat)abstract
- Soft tissue sarcomas (STS) are characterized by deregulated proliferation. Ki-67 is a cell cycle antigen which may be elevated in proliferative states. We analysed Ki-67 expression in fixed and embedded tissues from STS in order to examine associations between proliferation, primary tumour characteristics, and metastasis. One hundred and eighty-two adult patients with trunk wall or extremity STS were treated at our institution between 1980 and 1992 (35 developed local recurrence and 56 developed metastases). Median follow-up time for survivors was 6 years (1-13). We used a semiquantitative score to the assess percentage of Ki-67-positive cells: < or = 10% (n = 86), > 10-25% (n = 57), > 25-50% (n = 30), > 50-75% (n = 7), > 75-100% (n = 2). Increasing Ki-67 expression correlated positively with tumour size, malignancy grade, necrosis, vascular invasion, S-phase fraction, and metastasis. A Ki-67 index Ki-D < or = 10% (n = 86) and > 10% (n = 96) defined two groups who had 84% and 56% 3-year metastasis-free survival (p = 0.0001), respectively. Tumours with Ki-D > 10 were typically large, high grade, necrotic, DNA aneuploid, and had intravascular invasion and a higher S-phase fraction. Ki-67 expression may be helpful in predicting survival of patients with soft tissue sarcomas.
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| 10. |
- Eberhard, Anna, et al.
(författare)
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Predictors of unacceptable pain with and without low inflammation over 5years in early rheumatoid arthritis-an inception cohort study
- 2021
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesPain is a major symptom in patients with rheumatoid arthritis (RA). In early RA, pain is usually due to synovitis, but can also persist despite effective anti-inflammatory treatment. The objective of this study was to investigate the pain course over time and predictors of unacceptable pain and unacceptable pain with low inflammation, in patients with early RA.MethodsAn inception cohort of 232 patients with early RA, recruited in 1995-2005, was followed in a structured programme for 5years. Pain was assessed using a visual analogue scale (VAS; 0-100). Unacceptable pain was defined as VAS pain >40 based on the patient acceptable symptom state (PASS) and low inflammation as CRP <10mg/l. Baseline predictors of unacceptable pain were evaluated using logistic regression analysis.ResultsPain improved significantly during the first 6months, but then remained basically unchanged. Thirty-four per cent of the patients had unacceptable pain 5years after inclusion. Baseline predictors of unacceptable pain after 5years were lower swollen joint counts [odds ratio (OR) 0.71 per standard deviation (95% confidence interval (CI) 0.51-0.99)] and higher VAS for pain and global assessment of disease activity. Unacceptable pain with low inflammation after 5years was negatively associated with anti-CCP antibodies [OR 0.50 (95% CI 0.22-0.98)].ConclusionOver one third of the patients had unacceptable pain 5years after inclusion. Lower swollen joint count was associated with unacceptable pain at 5years. The results may be explained by the positive effects of treatment on pain related to inflammation. Non-inflammatory long-lasting pain appears to be a greater problem in anti-CCP-negative patients.
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