[Pediatric posterior fossa tumors]. / Infratentorielle Hirntumoren bei Kindern.

CLINICAL ISSUE: Tumors of the posterior fossa account for about 50-55% of brain tumors in childhood. DIAGNOSTIC WORKUP: The most frequent tumor entities are medulloblastomas, pilocytic astrocytomas, ependymomas, diffuse midline gliomas and atypical teratoid-rhabdoid tumors. Neuroradiological differential diagnosis with magnetic resonance imaging (MRI) is of considerable importance for preoperative planning as well as planning of follow-up therapy. PERFORMANCE: Most important findings for differential diagnosis of pediatric posterior fossa tumors are tumor location, patient age and the intratumoral apparent diffusion assessed by diffusion-weighted imaging. ACHIEVEMENTS: Advanced MR techniques like MRI perfusion and MR spectroscopy can be helpful both in the initial differential diagnosis and in tumor surveillance, but exceptional characteristics of certain tumor entities should be kept in mind. PRACTICAL RECOMMENDATIONS: Standard clinical MRI sequences including diffusion-weighted imaging are the main diagnostic tool in evaluating posterior fossa tumors in children. Advanced imaging methods can be helpful, but should never be interpreted separately from conventional MRI sequences.

TIMP4 Modulates ER-α Signalling in MCF7 Breast Cancer Cells.

Tissue inhibitor of metalloprotease 4 (TIMP4) contributes to poor prognosis in breast and other tumours. However, the mechanisms of how TIMP4 influences breast cancer cell behaviour are unknown. Our aim was to explore the signalling pathways modulated by TIMP4 in breast cancer cells. Human recombinant TIMP4 was added to MCF7 breast cancer cells and RNASeq was performed. TIMP4 RNASeq results were validated by RT-PCR. Network analyses of TIMP4-exposed cells showed that ER-α, HIF1A and TGF-ß signalling were activated, whereas FOXO3 signalling was downregulated. ER-α protein levels were increased and concordantly, promoters of TIMP4-upregulated genes were significantly enriched in oestrogen-binding sites. We concluded that TIMP4 modulates multiple signalling pathways relevant in cancer in MCF7 cells, including the ER-α cascade.

Gene regulation by BCL3 in a cervical cancer cell line.

BCL3 is a putative proto-oncogene deregulated in haematopoieitic and solid tumours. It has been suggested that its oncogenic effects could be mediated, at least in part, by inducing proliferation and inhibiting cell death. To provide more insight into the mediators of these effects, we used an unbiased approach to analyse the mRNA expression changes after knocking-down BCL3 using specific shRNAs. One hundred eighty genes were up-regulated and sixtynine genes were down-regulated after knocking down BCL3. Function analyses showed enrichment in genes associated with cellular growth and proliferation, cell death and gene expression. We found that STAT3, an important oncogene in human cancer, was the central node of one of the most significant networks. We validated STAT3 as a bona fide target of BCL3 by additional interference RNA and in silico analyses of previously reported lymphoma patients.

Participation of Omi Htra2 serine-protease activity in the apoptosis induced by cisplatin on SW480 colon cancer cells.

Apoptosis is triggered by two interconnected pathways, extrinsic and intrinsic. The intrinsic pathway is activated by genomic stress promoting mitochondrial release of apoptotic proteins. One of these proteins is Omi/Htra2, a serine protease which inactivates Inhibitor of Apoptosis Proteins (IAPs). In the present work, we assessed the participation of Omi/Htra2 in the cell death induced by the chemotherapeutic drugs 5-fluorouracil (5-FU) and cisplatin (CDDP) in SW480 colon cancer cells. CDDP and 5-FU induced apoptosis mediated by the intrinsic pathway in colon cancer cells, as demonstrated by morphological analyses, mitochondrial cytochrome c release and cleavage of caspase 3. Omi/Htra2 was also released from mitochondria of cells exposed to these drugs, as demonstrated by immunofluorescence and western blot assays of subcellular fractions. Exposure of cells to the Omi/Htra2 serine protease inhibitor UCF-101 prevented death p<0.0001 and partially suppressed reproductive cell death of cells exposed to cisplatin p<0.05, but not to 5-FU p=0.49. From these experiments we show that Omi/Htra2 serine protease activity participates in the cell death induced by CDDP but not of 5-FU in colon cancer cells.

Tumor HGF lacks prognostic significance in Mexican breast cancer patients.

Hepatocyte growth factor-scatter factor (HGF-SF) is a pleiotropic protein implicated in tumor formation and metastasis. Since increased levels of HGF-SF were first identified in breast cancer tissue or patient serum, some evidence has suggested that tumor or serum HGF-SF concentration could be one of the most accurate prognostic factors for this disease. However, other recent investigations have not been able to corroborate this finding. The study aims to establish the prognostic significance of HGF-SF in Mexican breast cancer women. Surgical specimens were obtained from 67 incident breast cancer patients at the Mexican National Cancer Institute between 1994 and 1995. Primary breast cancer tissue HGF-SF was measured by quantitative sandwich enzyme immunoassay. Relapse-free and overall survival curves were generated using Kaplan-Meier method. Significance of survival differences was calculated by log-rank test. chi2 was used for the association analysis between prognostic variables. Disease-free survival and overall survival were similar between the high tumor HGF group of patients and the low HGF patients (p = 0.7 and p = 0.36 respectively). No association was found between HGF and other clinicopathological variables (age, menopause status, clinical tumor size, clinical node involvement, metastasis, tumor grade, Estrogen Receptor and Progesterone Receptor). We found no prognostic significance for HGF, nor did we find a clear association between HGF and other known prognostic factors. A firm conclusion cannot be established regarding the role of HGF as a prognostic tool in breast cancer patients.