Meiotic gene activation in somatic and germ cell tumours.

BACKGROUND: Germ cell tumours are uniquely associated with the gametogenic tissues of males and females. A feature of these cancers is that they can express genes that are normally tightly restricted to meiotic cells. This aberrant gene expression has been used as an indicator that these cancer cells are attempting a programmed germ line event, meiotic entry. However, work in non-germ cell cancers has also indicated that meiotic genes can become aberrantly activated in a wide range of cancer types and indeed provide functions that serve as oncogenic drivers. Here, we review the activation of meiotic factors in cancers and explore commonalities between meiotic gene activation in germ cell and non-germ cell cancers. OBJECTIVES: The objectives of this review are to highlight key questions relating to meiotic gene activation in germ cell tumours and to offer possible interpretations as to the biological relevance in this unique cancer type. MATERIALS AND METHODS: PubMed and the GEPIA database were searched for papers in English and for cancer gene expression data, respectively. RESULTS: We provide a brief overview of meiotic progression, with a focus on the unique mechanisms of reductional chromosome segregation in meiosis I. We then offer detailed insight into the role of meiotic chromosome regulators in non-germ cell cancers and extend this to provide an overview of how this might relate to germ cell tumours. CONCLUSIONS: We propose that meiotic gene activation in germ cell tumours might not indicate an unscheduled attempt to enter a full meiotic programme. Rather, it might simply reflect either aberrant activation of a subset of meiotic genes, with little or no biological relevance, or aberrant activation of a subset of meiotic genes as positive tumour evolutionary/oncogenic drivers. These postulates provide the provocation for further studies in this emerging field.

Relative survival of patients with non-malignant central nervous system tumours: a descriptive study by the Austrian Brain Tumour Registry.

BACKGROUND: Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival. METHODS: We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival. RESULTS: Overall 5-year relative survival was 96.1% (95% CI 95.1-97.1%), being significantly lower in tumours of borderline (90.2%, 87.2-92.7%) than benign behaviour (97.4%, 96.3-98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%). CONCLUSION: The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.

Characterization of Bacillus subtilis spore inactivation in low-pressure, low-temperature gas plasma sterilization processes.

AIMS: To identify structural components of Bacillus subtilis spores serving as targets for sterilization with microwave induced low-pressure, low-temperature nitrogen-oxygen plasma. METHODS AND RESULTS: The inactivation of spores followed a biphasic kinetics consisting of a log-linear phase with rapid inactivation followed by a slow inactivation phase. In the course of plasma treatment, damage to DNA, proteins and spore membranes were observed by monitoring the occurrence of auxotrophic mutants, inactivation of catalase (KatX) activity and the leakage of dipicolinic acid, respectively. Spores of the wild-type strain showed the highest resistance to plasma treatment. Spores of mutants defective in nucleotide excision repair (uvrA) and small acid-soluble proteins (Delta sspA Delta sspB) were more sensitive than those defective in the coat protein CotE or spore photoproduct repair (splB). Exclusion of reactive particles and spectral fractions of UV radiation from access to the spores revealed that UV-C radiation is the most effective inactivation agent in the plasma, whereby the splB and Delta cotE mutant spores were equally and slightly less sensitive, respectively, than the wild-type spores. Finally, the extent of damages in the spore DNA determined by quantitative PCR correlated with the spore inactivation. CONCLUSIONS: Spore inactivation was efficiently mediated by a combination of DNA damage and protein inactivation. DNA was identified to be the primary target for spore inactivation by UV radiation emitted by the plasma. Coat proteins were found to constitute a protective layer against the action of the plasma. SIGNIFICANCE AND IMPACT OF THE STUDY: The results provide new evidence to the understanding of plasma sterilization processes. This knowledge supports the identification of useful parameters for novel plasma sterilization equipment to control process safety.

Characterisation of selected cadmium--zinc--telluride detectors.

The performance of new detection technologies like the ambient temperature cadmium--zinc--telluride (CdZnTe) detectors is of interest for search and identification of radioactive material in a range of applications. Various types of CdZnTe detectors that are currently available on the market as well as some specially designed ones were tested and characterised. The examination included peak shape, energy-resolution, energy-range and also the usability in hand-held applications. Additionally, the effects of the use of a cooling system were evaluated.

Carcinoma showing thymic-like elements--a rare malignancy of the thyroid gland.

BACKGROUND: Carcinoma showing thymic-like elements (CASTLE) is a rare tumour of the thyroid of thymic origin. The histological appearance of this tumour may be similar to that of squamous cell carcinoma of the thyroid, but outcome associated with CASTLE is more favourable. METHODS: A systematic literature review was conducted for case reports on CASTLE. A text word search of the Medline database was made with a manual search of the citations from these references. Twenty-two case reports were found. RESULTS: In five patients with tumour-negative lymph nodes no local or distant recurrence was observed. Seventeen patients had unknown or involved lymph nodes. Two patients were excluded from further study: one had no follow-up and one was treated by irradiation only. Of the remaining 15, six had local, three had distant and two had local and distant recurrence. In patients with involved or unknown lymph node status, local recurrence was noted in one of five patients treated by surgery and irradiation, and in seven of ten patients treated by surgery alone. Irradiation or systemic chemotherapy was given to four patients with recurrent tumours, with variable response. CONCLUSION: CASTLE with tumour-negative lymph nodes has a low risk of recurrence and surgery without adjuvant therapy is sufficient. Radiotherapy seems indicated when lymph nodes are tumour positive and can be effective for recurrent tumours. In selected patients surgery for recurrent tumour can improve quality of life and outcome.

[Predictive value of latex agglutination on Helicobacter pylori in children with recurrent abdominal pain]. / Praediktiver Wert einer Latex-Agglutination auf Helicobacter pylori bei Kindern mit rezidivierenden abdominellen Beschwerden.

In a prospective investigation, a rapid latex test for Helicobacter pylori in the serum (Pyloriset) was carried out in 39 patients with recurrent abdominal pain aged from six to 15 years. The test was positive in 19 patients. All of these children were subjected to gastroduodenoscopy. Seven cases showed a Helicobacter-associated chronic active antrum gastritis, whereas in the remaining 12 children gastritis not induced by Helicobacter or normal mucosa was found. Of the 20 Pyloriset-negative patients, only five could be biopsied. One of these showed a Helicobacter pylori-induced antrum gastritis. The latex test investigated had a positive predictive value which was too low (37%) to make it helpful in deciding for or against gastroduodenoscopy and the general anesthesia mostly associated with this.

Synovial metaplasia of the skin.

We present two female patients, aged 15 and 45 years, with synovial metaplasia of the skin. Both lesions, localized in the knee and hand respectively, arose after preceding local trauma. Case 1 had intradermal irregular cystic spaces in the adjacent myxoid stroma of which large polygonal eosinophilic cells were found. In contrast, case 2 was characterized by a longitudinal space within the lower dermis and subcutis which was lined by a membrane similar to hyperplastic synovium. The cells of the membrane showed an eosinophilic spindle shaped cytoplasm with processes towards the lumen. In both cases the eosinophilic cells, strongly suggestive of fibroblasts, showed staining for vimentin only, whereas no reactivity could be obtained with antibodies to actin, desmin, S-100 protein, Factor VIII related antigen, cytokeratin, epithelial membrane antigen, carcinoembryonic antigen and CD 68. The absence of CD 68 positivity differs from that seen in normal and hyperplastic synovium. Delayed wound healing around a nidus seems the most likely cause of the change.

[Urticarial vasculitis as a symptom of Muckle-Wells syndrome?]. / Urtikarielle Vaskulitis als Symptom des Muckle-Wells-Syndroms?

A patient is reported with a history of several years of chronic urticaria, transient fever, arthralgias and secondary systemic amyloidosis. A biopsy of an urticarial lesion showed necrotizing vasculitis and amyloid deposits in the eccrine sweat glands. Amyloid A deposits were also detected in kidney and rectum biopsies. This patient is likely to represent a variant of the Muckle-Wells syndrome (chronic relapsing urticaria, fever, arthralgia, deafness and renal amyloidosis). Hitherto undescribed is the presence of a necrotizing vasculitis as cause of the urticarial rash; further investigation will determine whether or not this finding represents the rule rather than an exception.

Cystectomy: the treatment of choice in patients with carcinoma in situ of the urinary bladder?

Patients (n = 46) with carcinoma in situ (Tis) of the urinary bladder were treated by intravesical chemotherapy. The complete remission rate was 75%. After a mean interval of 17 months recurrent tumours were diagnosed in 47%. Radical cystectomy with urethrectomy was performed in eight patients. Distal ureterectomy and uretercystoneostomy was done in six patients because of a distal ureteric tumour. Based on this group of 46 patients and the current literature, the following criteria are essential in indicating cystectomy: (1) micro-invasion; (2) persistent Tis after adequate intravesical treatment; (3) progressive tumour; (4) Tis of ureter and/or prostate; (5) tumour recurrence at more advanced stage.

[Xanthogranulomatous pyelonephritis in early childhood]. / Xanthogranulomatöse Pyelonephritis im Kleinkindesalter.

We report on a two-year-old infant boy in whom a tumorous enlargement of the left kidney which was not imaged in the excretion urogram was discovered by renal sonography after the second urinary tract infection. By synopsis of the clinical data and imaging techniques, but especially by the detection of foam cells in the urinary sediment, we were already able to make the diagnosis of a xanthogranulomatous pyelonephritis before the operation. Since diffuse infiltration of the entire organ was present, total nephrectomy was carried out as the therapy of choice. Besides the case report, in particular the difficulties in the diagnosis of this form of pyelonephritis (especially in infancy) are described.

Interactions between bladder tumor cells as tumor spheroids from the cell line J82 and human endothelial cells in vitro.

Multicellular tumor spheroids (MCTS) are a reliable model of nonvascularized tumor cell aggregates showing a well defined three-dimensional growth pattern and are comparable with small metastatic cancer cell complexes in blood circulation. In the present study we have established a co-culture system of multicellular bladder tumor spheroids with human endothelial cells on extracellular matrix (ECM) in order to investigate morphological and proliferative changes of endothelial and tumor cells within a defined time of cell-cell interaction. The MCTS--endothelial cell--extracellular matrix complex was observed within coculture periods from 1/2 to seven days. Morphological changes (light microscopy, scanning and electron microscopy) indicated that MCTS are not influenced by cocultured endothelial cells. The tumor cells invaded into the ECM after degradation of endothelial cells in the center of the contact zone. Endothelial cells, however, showed degenerative changes as well as a complex reaction in their proliferation activities. We could recognize an initial increase of proliferation of endothelial cells next to the MCTS. Later on, endothelial cells next to invading tumor cells showed changes in morphological polarity. The model system used has the advantage of using human tumor tissue. It distinguishes between basic cellular mechanisms like adherence, migration, DNA synthesis and proliferation in the study of the contact of tumor cells and vascular endothelial cells as an important event in hematogenous tumor spread.

Melanocytic neuroendocrine carcinoma of the thymus.

A neuroendocrine carcinoma of the thymus with an ectopic adrenocorticotropic hormone (ACTH) syndrome and melanocytic differentiation is described. ACTH, neuron-specific enolase (NSE) and S-100 protein were identified in the tumor by immunocytochemistry. Neurosecretory granules and melanosomes could be demonstrated in different cell populations by electronmicroscopy. The clinicopathologic findings are presented. The literature is briefly discussed.

Multicellular bladder tumor spheroids in coculture with human endothelial cell monolayers.

Multicellular tumor spheroids (MCTS) are avascular spherical tumors grown systematically out of single cells in vitro. The coculture of MCTS of the human bladder carcinoma cell line J 82 with confluent human endothelial cell layers serves as a model to study cell-cell interactions as an important feature in hematogenous tumor spread. Basic information is obtained by phase contrast microscopy and histochemistry. More detailed information is given by the application of scanning and transmission electron microscopy. Immunohistochemistry helps to differentiate endothelial cells from tumor cells (factor VIII-related antigen). The application of this coculture model and of the various methods of evaluation enables us to study cell-to-cell contact phenomena systematically.

Preparation of monolayer smears from paraffin-embedded tissue for image cytometry.

A method is described for the preparation of monolayer smears from paraffin-embedded tissue suitable for automated image analysis and DNA measurements. The proposed technique uses enzyme treatment and syringing for cell dispersal. Slide preparation is performed by centrifugal cytology. After Feulgen staining the quality of the monolayer smears is sufficiently high to enable visual morphologic evaluation. Automated DNA measurements using the Leyden television analysis system (LEYTAS) show coefficients of variation (CV) of 4.5% for the diploid cell population of the suspended tissue. This is approximately the same as the CV in fresh material from the same tumor. Formalin fixed trout red blood cells are used as reference cells. By applying image cytometry to paraffin-embedded tissue this method allows retrospective studies of, for instance, the significance of DNA content with regard to the behavior of a tumor.