The successful translation of therapies targeting signal-transduction pathways that are activated by oncogenes has provided a model for molecularly targeted therapy, and the identification of mutations in v-raf murine sarcoma viral oncogene homolog B1 (BRAF), a serine/threonine kinase, has turned the attention of the melanoma field toward this concept. »
07/13/10

A modified form of high dose rate (HDR) brachytherapy has been developed called Axxent Electronic Brachytherapy (EBT). EBT uses a kilovolt X-ray source and does not require treatment in a shielded vault or a HDR afterloader unit. A multi-center clinical study was carried out to evaluate the success of treatment delivery, safety and toxicity of EBT in patients with endometrial cancer. »
07/20/10

Tumor cell invasion into adjacent normal brain is a mesenchymal feature of GBM and a major factor contributing to their dismal outcomes. Therefore, better understandings of mechanisms that promote mesenchymal change in GBM are of great clinical importance to address invasion. We previously showed that the bHLH transcription factor TWIST1 which orchestrates carcinoma metastasis through an epithelial mesenchymal transition (EMT) is upregulated in GBM and promotes invasion of the SF767 GBM cell line in vitro. »
07/20/10

Activation of the extrinsic apoptosis pathway by tumour necrosis factor related apoptosis inducing ligand (TRAIL) is a novel therapeutic strategy for treating cancer that is currently under clinical evaluation. Identification of molecular biomarkers of resistance is likely to play an important role in predicting clinical anti tumour activity. The involvement of the mitochondrial type 1 voltage dependent anion channel (VDAC1) in regulating apoptosis has been highly debated. To date, a functional role in regulating the extrinsic apoptosis pathway has not been formally excluded. »
07/20/10

Pancreatic ductal adenocarcinoma shows a distinct apoptosis resistance, which contributes significantly to the aggressive nature of this tumor and constrains the effectiveness of new therapeutic strategies. Apoptosis resistance is determined by the net balance of the cells pro- and anti-apoptotic "control mechanisms". Numerous dysregulated anti-apoptotic genes have been identified in pancreatic cancer and seem to contribute to the high anti-apoptotic buffering capacity. We aimed to compare the benefit of simultaneous gene silencing (SGS) of several candidate genes with conventional gene silencing of single genes. »
07/20/10

Metastasis represents a major adverse step in the progression of breast carcinoma. Lymph node invasion is the most relevant prognostic factor; however little is known on the molecular events associated with lymph node metastasis process. This study is to investigate the status and role of methylation in lymph node metastatic tumors. Materials and methods: Bisulfite pyrosequencing is used to screen 6 putative tumor suppressor genes (HIN-1, RASSF1A, RIL, CDH13, RARbeta2 and E-cadherin) in 38 pairs of primary breast tumors and lymph node metastases. »
07/20/10

DeltaNp63 alpha is an epithelial progenitor cell marker that maintains epidermal stem cell self-renewal capacity. Previous studies revealed that UV-damage induced p53 phosphorylation is confined to DeltaNp63 alpha-positive cells in the basal layer of human epithelium. »
07/21/10

Histone deacetylase (HDAC) inhibitors are a novel anti-tumor therapy. To determine whether HDAC inhibitors may be useful in the treatment of adult acute lymphoblastic leukemia (ALL), we examined the acetylation of histone H4 by immunohistochemistry in newly diagnosed ALL patients and evaluated the impact of acetylation on complete remission (CR) rate, relapse-free survival (RFS), and overall survival (OS). »
07/21/10

Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation. »
07/21/10

Neuroendocrine (NE) differentiation in prostate cancer has been correlated with a poor prognosis and hormone refractory disease. In a previous report, we demonstrated the presence of immunoreactive cytoplasmic hypoxia inducible factor 1alfa (HIF1alfa), in both benign and malignant NE prostate cells. HIF1alfa and HIF1beta are two subunits of HIF1, a transcription factor important for angiogenesis. The aim of this study was to elucidate whether the cytoplasmic stablization of HIF1alfa in androgen-independent NE differentiated prostate cancer is due to the presence of certain HIF1alfa isoforms. »
07/21/10