Rikke Kølby Christensen

Evaluation of p16INK4a/Ki-67 dual stain in comparison with an mRNA human papillomavirus test on liquid-based cytology samples with low-grade squamous intraepithelial lesion

The objective of the current study was to investigate the clinical performance of detecting high‐grade lesions with the CINtec PLUS p16INK4a/Ki‐67 dual stain and the APTIMA human papillomavirus (HPV) Assay in a cohort of women with low‐grade squamous intraepithelial lesion (LSIL) cytology. The authors also assessed the reproducibility of the evaluation of immunocytochemical staining.

Value of fine-needle aspiration biopsy of salivary gland lesions

The aim of this study was to assess the utility of fine‐needle aspiration biopsy (FNAB) in the diagnosis and treatment planning of the lesions of the salivary gland.

Transformation of human mesenchymal stem cells in radiation carcinogenesis: long-term effect of ionizing radiation

Increasing evidence on cancer stem cells suggest that stem cells are susceptive to carcinogenesis and consequently can be the origin of many cancers. We have recently established a telomerase-transduced human mesenchymal stem cell line and subsequently irradiated this in order to achieve malignant transformation. In the present study, we analyzed the long-term effect of ionizing radiation on these cells and investigate whether radiation can trigger tumor development. The cells were irradiated with a low (2.5 Gy) and a high (15 Gy) dose of gamma-rays and followed for up to 6 months after radiation. A subclone of the cells irradiated with 2.5 Gy of gamma-rays formed tumors after implantation to severe combined immunodeficiency mice. During the process of transformation, the cells showed accelerated telomere shortening, increased levels of anaphase bridges and a shift from balanced to unbalanced translocations. The tumor suppressor genes p53 and p21(CIP1) functioned normally throughout the study. Our observations indicate that radiation destabilized the telomeres and that the presence of uncapped telomeres initiated fusion-break-fusion cycles, resulting in increased chromosomal instability and tumor formation. Thus, bone marrow-derived human mesenchymal stem cells are capable of exhibiting a malignant phenotype.

Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

BackgroundTissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may therefore play an essential role in the progression of a malignant tumour.The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment in the individual patient.MethodsTIMP-1 was assessed by immunohistochemistry (in tissue micro arrays) in a total of 163 ovarian cancer specimens obtained from primary debulking surgery during 1991-1994 as part of a randomized clinical protocol.ResultsPositive TIMP-1 immunoreactivity was found in 12.3% of the tumours. The median survival time for the 143 patients with TIMP-1 negative tumours was 23.7 months [19.0-29.4] 95% CI, while the median survival time for the 20 patients with TIMP-1 positive tumours was 15.9 months [12.3-27.4] 95% CI. Although a difference of 7.8 months in median overall survival in favor of the TIMP-1 tumour negative patients was found, this difference did not reach statistical significance (p = 0.28, Kaplan-Meier, log-rank test). Moreover, TIMP-1 immunoreactivity was not associated with CA125 response (p = 0.53) or response at second look surgery (p = 0.72).ConclusionTIMP-1 immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy.

Evaluation of p16INK4a/Ki-67 dual stain in comparison with an mRNA human papillomavirus test on liquid-based cytology samples with low-grade squamous intraepithelial lesion: p16INK4a/Ki-67 Dual Staining in LSIL

The objective of the current study was to investigate the clinical performance of detecting high‐grade lesions with the CINtec PLUS p16INK4a/Ki‐67 dual stain and the APTIMA human papillomavirus (HPV) Assay in a cohort of women with low‐grade squamous intraepithelial lesion (LSIL) cytology. The authors also assessed the reproducibility of the evaluation of immunocytochemical staining.

Evaluation of p16INK4a/Ki-67 dual stain in comparison with an mRNA human papillomavirus test on liquid-based cytology samples with low-grade squamous intraepithelial lesion: Cancer Cytopathology

The objective of the current study was to investigate the clinical performance of detecting high‐grade lesions with the CINtec PLUS p16INK4a/Ki‐67 dual stain and the APTIMA human papillomavirus (HPV) Assay in a cohort of women with low‐grade squamous intraepithelial lesion (LSIL) cytology. The authors also assessed the reproducibility of the evaluation of immunocytochemical staining.

Transformation of Mesenchymal Stem Cells

As part of normal organismal homeostasis, the human body loses various types of cells like hepatocytes, keratinocytes and certain types of blood cells and needs to replace them. These cells are replaced using stem cells as the source. Many different names are used for cells with stem cell-like properties, such as precursor cells, progenitor cells, somatic stem cells and adult stem cells. Stem cells are unique cells that have the ability to renew themselves through mitotic cell division and differentiate into a diverse range of specialized cell types. In addition, stem cells, with few notable exceptions, are cell types that show telomerase activity and therefore, actively maintain telomere length to some degree. The ability to maintain telomere length allows them to have an extended proliferative capacity compared to somatic cells. There are three kinds of stem cells: Embryonic, germinal and somatic or in other terms adult stem cells. The differentiation potential of stem cells varies according to type from totipotency to unipotency. Cells such as the fertilized oocytes, up to the 8-cell blastocyst, are considered to be totipotent since they can differentiate and generate a complete organism. Embryonic stem (ES) cells are derived from the inner cell mass of a blastocyst. ES cells posses all the characteristics of true stem cells. In addition to the self-renewal capacity, they are pluripotent, being able to produce derivates of all three germ layers (endoderm, mesoderm and ectoderm) but not the complete organism (Burdon et al., 2002). A high telomerase activity prevents the ES cells from undergoing crisis and reaching senescence, which is an advantage for long-term culturing. ES cells have furthermore been shown to retain their developmental identity even after reintroduction into the blastocyst (Beddington & Robertson, 1989). Somatic stem cells are differentiated forms of embryonic stem cells that are known as multipotent stem cells. They are capable of self-renewal and are responsible for the regenerative property of the e.g. hematopoietic system and the gastrointestinal system. These cells can be isolated from the developing organism (the fetus and the postnatal organism) as well as from the adult organism. Depending on their origin, the offspring of the somatic stem cells is also specific to the original tissue. A stem cell is said to be unipotent like the epidermal stem cells if they can persistently give rise to only a specific cell type. It has for many years been known that stem cells – contrary to other cell types –