49 research outputs found

    Rapid interphase and metaphase assessment of specific chromosomal changes in neuroectodermal tumor cells by in situ hybridization with chemically modified DNA probes

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    Repeated DNAs from the constitutive heterochromatin of human chromosomes 1 and 18 were used as probes in nonradioactive in situ hybridization experiments to define specific numerical and structural chromosome aberrations in three human glioma cell lines and one neuroblastoma cell line. The number of spots detected in interphase nuclei of these tumor cell lines and in normal diploid nuclei correlated well with metaphase counts of chromosomes specifically labeled by in situ hybridization. Rapid and reliable assessments of aneuploid chromosome numbers in tumor lines in double hybridization experiments were achieved, and rare cells with bizarre phenotype and chromosome constitution could be evaluated in a given tumor cell population. Even with suboptimal or rare chromosome spreads specific chromosome aberrations were delineated. As more extensive probe sets become available this approach will become increasingly powerful for uncovering various genetic alterations and their progression in tumor cells

    TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC trial): Study protocol for a randomized controlled trial

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    Background: Cervical intraepithelial neoplasia (CIN) is the premalignant condition of cervical cancer. Whereas not all high grade CIN lesions progress to cervical cancer, the natural history and risk of progression of individual lesions remain unpredictable. Therefore, high-grade CIN is currently treated by surgical excision: large loop excision of the transformation zone (LLETZ). This procedure has potential complications, such as acute haemorrhage, prolonged bleeding, infection and preterm birth in subsequent pregnancies. These complications could be prevented by development of a non-invasive treatment modality, such as topical imiquimod treatment. The primary study objective is to investigate the efficacy of topical imiquimod 5 % cream for the treatment of high-grade CIN and to develop a biomarker profile to predict clinical response to imiquimod treatment. Secondary study objectives are to assess treatment side-effects, disease recurrence and quality of life during and after different treatment modalities. Methods/design: The study design is a randomized controlled trial. One hundred fort

    Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial

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    The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia (CIN). The lagging inclusions were mainly due to a strong patient preference for either of the two treatment modalities. This prompted us to initiate a new study on the same subject, with a non-randomized, open-label design: the 'TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC)-3' study. Original TOPIC-trial: Medical Ethics Committee approval number METC13231; ClinicalTrials.gov Identifier: NCT02329171, 22 December 2014. TOPIC-3 study: Medical Ethics Committee approval number METC162025; ClinicalTrials.gov Identifier: NCT02917746, 16 September 2016.

    Chromosome aberrations in adenomas of the colon. Proof of trisomy 7 in tumor cells by combined interphase cytogenetics and immunocytochemistry

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    Chromosome aberrations in adenomas of the colon. Proof of trisomy 7 in tumor cells by combined interphase cytogenetics and immunocytochemistry. Herbergs J, de Bruine AP, Marx PT, Vallinga MI, Stockbrugger RW, Ramaekers FC, Arends JW, Hopman AH. Department of Pathology, University Hospital, Maastricht, The Netherlands. Thirty-five colon adenomas from 26 patients were analyzed with centromeric probes for chromosomes 1, 7, 17, X and Y in order to study numerical aberrations, chromosome imbalances, aneuploidy and tetraploidization. The fluorescent in situ hybridization (FISH) technique was applied to single-cell suspensions and a combination of FISH and immunocytochemistry (ICC) was employed to identify the cell type under study. Trisomy of chromosome 7 was detected in 37% of the cases. In 7 out of 13 cases this aberration was combined with abnormalities of one or 2 of the other investigated chromosomes. No correlation could be demonstrated between any of the detected chromosomal aberrations and size, localization or degree of epithelial dysplasia. With the combined FISH/ICC procedure, the abnormal cells were shown to be of epithelial rather than of stromal origin. Our data indicate that trisomy 7 is a common chromosome aberration in the epithelial component of colon adenoma

    Gain of chromosome 7, as detected by in situ hybridization, strongly correlates with shorter survival in astrocytoma grade 2.

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    The clinical course of astrocytoma grade 2 (A2) is highly variable and is not reflected by morphological characteristics. Earlier studies using small series of A2 cases suggest that in situ hybridization (ISH) with chromosome-specific DNA probes allows for frequent detection of aneusomy 1, trisomy 7, and monosomy 10. The role of trisomy 7 in astrocytoma carcinogenesis is disputed, however, because of its presence in non-neoplastic brain tissue, as detected by karyotyping. Our objective was to investigate whether there was a correlation between chromosomal aberrations and survival in a series of 47 cases of A2. All cases were evaluated for numerical aberrations of chromosomes 1, 7, and 10 by ISH. Chromosomal aberrations were detected in 68% of cases of A2. Trisomy/polysomy 7 was seen in 31 cases (66%), 22 of which (47%) had a high percentage of this numerical aberration. Only 11 of these 22 cases also showed aneusomy for I or 10. No cells or only a few cells with aberrations were detected in non-neoplastic control samples. Using Kaplan-Meier analysis, trisomy/polysomy 7 correlated significantly with shorter survival. Hence, as determined by ISH, trisomy/polysomy 7 is absent in non-neoplastic brain tissue and is frequently detected in A2, correlating with the malignant progression of the disease
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