Reduced risk of synovial sarcoma in females: X-chromosome inactivation?

Synovial sarcoma shows a characteristic t(X;18) translocation but not the expected female predominance in incidence. We speculate that, among females, one X-chromosome is inactivated and that only the translocation to an active X-chromosome leads to development of synovial sarcoma. Population-based cancer registry data from the SEER program support this hypothesis

Metastatic potential of an aneurysmal bone cyst

Aneurysmal bone cysts (ABCs) are benign bone tumors consisting of blood-filled cavities lined by connective tissue septa. Recently, the hypothesis that ABCs are lesions reactive to local hemodynamics has been challenged after the discovery of specific recurrent chromosomal abnormalities. Multiple cases of malignant transformation of ABC into (osteo)sarcoma have been described, as well as a number of cases of telangiectatic osteosarcoma which had been misdiagnosed as ABC. We herewith document a case of a pelvic ABC metastatic to the lung, liver, and kidneys. Diagnosis was confirmed by the presence of a break in the USP6 gene, which is pathognomonic for ABC, in a pulmonary metastasis of our patient. Sarcomatous transformation as an explanation for this behavior was ruled out by demonstrating diploid DNA content in both the pulmonary lesion and the primary tumor

Absence of polysialylated NCAM is an unfavorable prognostic phenotype for advanced stage neuroblastoma

<p>Abstract</p> <p>Background</p> <p>The expression of a neural crest stem cell marker, polysialic acid (polySia), and its main carrier, neural cell adhesion molecule (NCAM), have been detected in some malignant tumors with high metastatic activity and unfavorable prognosis, but the diagnostic and prognostic value of polySia-NCAM in neuroblastoma is unclear.</p> <p>Methods</p> <p>A tumor tissue microarray (TMA) of 36 paraffin-embedded neuroblastoma samples was utilized to detect polySia-NCAM expression with a polySia-binding fluorescent fusion protein, and polySia-NCAM expression was compared with clinical stage, age, <it>MYCN </it>amplification status, histology (INPC), and proliferation index (PI).</p> <p>Results</p> <p>PolySia-NCAM-positive neuroblastoma patients had more often metastases at diagnosis, and polySia-NCAM expression associated with advanced disease (<it>P </it>= 0.047). Most interestingly, absence of polySia-NCAM-expressing tumor cells in TMA samples, however, was a strong unfavorable prognostic factor for overall survival in advanced disease (<it>P </it>= 0.0004), especially when <it>MYCN </it>was not amplified. PolySia-NCAM-expressing bone marrow metastases were easily detected in smears, aspirates and biopsies.</p> <p>Conclusion</p> <p>PolySia-NCAM appears to be a new clinically significant molecular marker in neuroblastoma, hopefully with additional value in neuroblastoma risk stratification.</p

Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n = 19,723) with normal fetal adrenal single-cell transcriptomes (n = 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues

Teachers' ideas versus experts' descriptions of 'the good teacher' in postgraduate medical education: implications for implementation. A qualitative study

Contains fulltext : 96394.pdf (publisher's version ) (Open Access)BACKGROUND: When innovations are introduced in medical education, teachers often have to adapt to a new concept of what being a good teacher includes. These new concepts do not necessarily match medical teachers' own, often strong beliefs about what it means to be a good teacher.Recently, a new competency-based description of the good teacher was developed and introduced in all the Departments of Postgraduate Medical Education for Family Physicians in the Netherlands. We compared the views reflected in the new description with the views of teachers who were required to adopt the new framework. METHODS: Qualitative study. We interviewed teachers in two Departments of Postgraduate Medical Education for Family Physicians in the Netherlands. The transcripts of the interviews were analysed independently by two researchers, who coded and categorised relevant fragments until consensus was reached on six themes. We investigated to what extent these themes matched the new description. RESULTS: Comparing the teachers' views with the concepts described in the new competency-based framework is like looking into two mirrors that reflect clearly dissimilar images. At least two of the themes we found are important in relation to the implementation of new educational methods: the teachers' identification and organisational culture. The latter plays an important role in the development of teachers' ideas about good teaching. CONCLUSIONS: The main finding of this study is the key role played by the teachers' feelings regarding their professional identity and by the local teaching culture in shaping teachers' views and expectations regarding their work. This suggests that in implementing a new teaching framework and in faculty development programmes, careful attention should be paid to teachers' existing identification model and the culture that fostered it

How Reliable Is Ki-67 Immunohistochemistry in Grade 2 Breast Carcinomas? A QA Study of the Swiss Working Group of Breast- and Gynecopathologists

Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. Methods Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. Results The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56–0.72). However, we found very high inter-observer variabilities (Kappa 0.04–0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01–0.04) and intra-observer agreement was likewise poor (Kappa 0.00–0.35). Conclusion Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas

Synthetic Mimic of Antimicrobial Peptide with Nonmembrane-Disrupting Antibacterial Properties

Proteolysis in dairy lactic acid bacteria has been studied in great detail by genetic, biochemical and ultrastructural methods. From these studies the picture emerges that the proteolytic systems of lactococci and lactobacilli are remarkably similar in their components and mode of action. The proteolytic system consists of an extracellularly located serine-proteinase, transport systems specific for di-tripeptides and oligopeptides (> 3 residues), and a multitude of intracellular peptidases. This review describes the properties and regulation of individual components as well as studies that have led to identification of their cellular localization. Targeted mutational techniques developed in recent years have made it possible to investigate the role of individual and combinations of enzymes in vivo. Based on these results as well as in vitro studies of the enzymes and transporters, a model for the proteolytic pathway is proposed. The main features are: (i) proteinases have a broad specificity and are capable of releasing a large number of different oligopeptides, of which a large fraction falls in the range of 4 to 8 amino acid residues; (ii) oligopeptide transport is the main route for nitrogen entry into the cell; (iii) all peptidases are located intracellularly and concerted action of peptidases is required for complete degradation of accumulated peptides.