Deregulation of miR-126 expression in colorectal cancer pathogenesis and its clinical significance

In this study, we investigated the expression profiles and clinicopathological significance of miR-126 in large cohort of patients with colorectal cancers as well the cellular repercussions of miR-126 in colon cancer cells along with its targets in-vitro. Down regulation of miR-126 expression was associated with histological subtypes, peri-neural tumour infiltration, microsatellite instability and pathological staging of colorectal cancers (p<0.05). Low miR-126 expression was also associated with poorer survival in patients with colorectal cancer. Analysis of matched tissues from the same patient revealed that approximately 70% of the tested patients had similar levels of expression of miR-126 in primary cancer and cancer metastases in both lymph node and distant metastases. In addition, induced overexpression of miR-126 showed reduced cell proliferation, increased apoptosis and decreased accumulation of cells in the G0-G1 phase of the colon cancer cells. Furthermore, SW480(+miR-126) cells showed reduced BCL-2 and increased P53 protein expression. To conclude, deregulation of miR-126 in colorectal cancer at the tissue and cellular levels as well as its correlation with various clinicopathological parameters confirm the cancer suppressive role of miR-126 in colorectal cancer.

Intraosseous schwannoma mimicking a periapical lesion on the adjacent tooth: Case report

Aim: To present an additional case of intraosseous schawannoma involving the apical area in the mandibular alveolar bone mimicking an inflammatory periapical lesion. Summary: This article describes a case of schwannoma periapically located mimicking an inflammatory periapical lesion in the mandible of a 34-year-old female. Diagnostic and therapeutic problems can occur when this lesion is misinterpreted as being endodontic in origin. The diagnosis, radiograph, immunohistochemical aspects and treatment are also discussed. Key learning points: • Intraosseous schwannoma is a rare unilocular radiolucency that when located periapically could be misdiagnosed as an endodontic lesion and result in unnecessary root canal treatment. • The vitality of the pulp is an important test to exclude lesions of inflammatory origin. • Histological examination is important to establish the diagnosis of lesions in the periradicular region. © 2007 International Endodontic Journal.

Pro-neural transcription factors as cancer markers

BACKGROUND: The aberrant transcription in cancer of genes normally associated with embryonic tissue differentiation at various organ sites may be a hallmark of tumour progression. For example, neuroendocrine differentiation is found more commonly in cancers destined to progress, including prostate and lung. We sought to identify proteins which are involved in neuroendocrine differentiation and differentially expressed in aggressive/metastatic tumours.

RESULTS: Expression arrays were used to identify up-regulated transcripts in a neuroendocrine (NE) transgenic mouse model of prostate cancer. Amongst these were several genes normally expressed in neural tissues, including the pro-neural transcription factors Ascl1 and Hes6. Using quantitative RT-PCR and immuno-histochemistry we showed that these same genes were highly expressed in castrate resistant, metastatic LNCaP cell-lines. Finally we performed a meta-analysis on expression array datasets from human clinical material. The expression of these pro-neural transcripts effectively segregates metastatic from localised prostate cancer and benign tissue as well as sub-clustering a variety of other human cancers.

CONCLUSION: By focussing on transcription factors known to drive normal tissue development and comparing expression signatures for normal and malignant mouse tissues we have identified two transcription factors, Ascl1 and Hes6, which appear effective markers for an aggressive phenotype in all prostate models and tissues examined. We suggest that the aberrant initiation of differentiation programs may confer a selective advantage on cells in all contexts and this approach to identify biomarkers therefore has the potential to uncover proteins equally applicable to pre-clinical and clinical cancer biology.

Neural stem cells, inflammation and NF-kappaB: basic principle of maintenance and repair or origin of brain tumours?

Several recent reports suggest that inflammatory signals play a decisive role in the self-renewal, migration and differentiation of multipotent neural stem cells (NSCs). NSCs are believed to be able to ameliorate the symptoms of several brain pathologies through proliferation, migration into the area of the lesion and either differentiation into the appropriate cell type or secretion of anti-inflammatory cytokines. Although NSCs have beneficial roles, current evidence indicates that brain tumours, such as astrogliomas or ependymomas are also caused by tumour-initiating cells with stem-like properties. However, little is known about the cellular and molecular processes potentially generating tumours from NSCs. Most pro-inflammatory conditions are considered to activate the transcription factor NF-kappaB in various cell types. Strong inductive effects of NF-kappaB on proliferation and migration of NSCs have been described. Moreover, NF-kappaB is constitutively active in most tumour cells described so far. Chronic inflammation is also known to initiate cancer. Thus, NF-kappaB might provide a novel mechanistic link between chronic inflammation, stem cells and cancer. This review discusses the apparently ambivalent role of NF-kappaB: physiological maintenance and repair of the brain via NSCs, and a potential role in tumour initiation. Furthermore, it reveals a possible mechanism of brain tumour formation based on inflammation and NF-kappaB activity in NSCs.

Granular cell tumour (Abrikossoff's tumour): Case series

This case series describes three unreported cases of an uncommon benign neoplasm named Abrikossoff's tumour or granular cell tumour (GCT). This mesenchymal neoplasm apparently arises from neural or Schwann cell origin with benign and malignant forms. All cases presented here were unique nodules on oral mucosa, coming out from the connective tissue, and occurring in women with age ranging from 30 to 42 years. The histological aspects of the GCT showed large granular cells arranged in groups and nests of connective tissue separating pseudoepitheliomatous overlying surface. This feature can possibly be misunderstood with squamous cell carcinoma. The differentiation between malignant and benign GCT is evaluated by the presence of metastases which is considered the only reliable criterion for malignancy. © 2005 Elsevier Ltd. All rights reserved.

Language outcomes subsequent to treatment of brainstem tumour in childhood

While the occurrence and management of brainstem tumours in children would not traditionally indicate potential direct structural impact on classical language centres, recent theories have implicated some involvement of the brainstem in a functional language and cognitive neural loop between the cerebellum and the cerebral hemispheres. Thus, the present paper explored the impact of treatment for brainstem tumour on the general and high-level language abilities of six children treated for brainstem tumour, in addition to phonological awareness skills. Group analysis revealed that children treated for brainstem tumour demonstrated intact language and phonological awareness abilities in comparison to an age- and gender-matched control group. Individual analysis revealed only one of six children treated for brainstem tumour revealed evidence of language disturbances, with an additional child demonstrating an isolated mildly reduced score on one phonological awareness task. Language deficits identified in a child treated with a combination of both radiotherapy and chemotherapy were noted in the high-level language area of lexical generation. Findings highlighted that no overt language disturbances were evident in children treated for brainstem tumour. However, further analysis into higher-level language skills in the present study indicated that both general and high-level language abilities require long-term monitoring in this population.

Oral granular cell tumour of the lip in an adult patient

Oral granular cell tumour is a rare soft tissue tumour of mesenchymal origin. The most frequently affected site in the oral cavity is the tongue, followed by the floor of mouth, and buccal mucosa. In paediatric patients, 25% of cases have been reported to occur in the lip, but this presentation in adults is extremely rare. We report a case of oral granular cell tumour in a 35 year-old female, located in the lower lip. Histopathological examination revealed eosinophilic granular cells which stained positively for S-100 protein; a finding supportive of a neural origin. A history of trauma was elicited in this case, and the lesion was treated with surgical excision.

Brain tumour stem cells

The dogma that the genesis of new cells is a negligible event in the adult mammalian brain has long influenced our perception and understanding of the origin and development of CNS tumours. The discovery that new neurons and glia are produced throughout life from neural stem cells provides new possibilities for the candidate cells of origin of CNS neoplasias. The emerging hypothesis is that alterations in the cellular and genetic mechanisms that control adult neurogenesis might contribute to brain tumorigenesis, thereby allowing the identification of new therapeutic strategies.