Home About us Contact
|
Home About us Contact | ||
|
|
||
High-grade Malignancy (high-grade + malignancy)
Selected AbstractsCeramide levels are inversely associated with malignant progression of human glial tumorsGLIA, Issue 2 2002Laura Riboni Abstract Ceramide represents an important sphingoid mediator involved in the signaling pathways that control cell proliferation, differentiation, and death. To determine whether ceramide levels correlate with the malignant progression of human astrocytomas, we investigated these levels in surgical specimens of glial tumors of low-grade and high-grade malignancy. Tumor samples obtained from 52 patients who underwent therapeutic removal of primary brain tumors were used. The tumors were classified according to standard morphologic criteria and were grouped into tumors of low-grade and high-grade malignancy. Sections of normal brain tissue adjacent to the tumor were also analyzed in 11 of the 52 patients. After extraction and partial purification, ceramide was measured by quantitative derivatization to ceramide-1-phosphate using diacylglycerol kinase and [,- 32P]ATP. Ceramide levels were significantly lower in the combined high-grade tumors compared with low-grade tumors and in both tumor groups compared with peritumoral tissue. The results indicate an inverse correlation between the amount of ceramide and tumor malignancy as assessed by both the histological grading and ganglioside pattern. Moreover, overall survival analysis of 38 patients indicates that ceramide levels are significantly associated with patient survival. The present findings indicate that ceramide is inversely associated with malignant progression of human astrocytomas and poor prognosis. The downregulation of ceramide levels in human astrocytomas emerges as a novel alteration that may contribute to glial neoplastic transformation. The low ceramide levels in high-grade tumors may provide an advantage for their rapid growth and apoptotic resistant features. This study appears to support the rationale for the potential benefits of a ceramide-based chemotherapy. GLIA 39:105,113, 2002. © 2002 Wiley-Liss, Inc. [source] L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancerPATHOLOGY INTERNATIONAL, Issue 1 2009Takeshi Sakata To find reliable biomarkers for high-grade malignancy, the relationship between immunohistochemical L-type amino-acid transporter 1 (LAT1) expression of biopsy samples, determined with the newly developed monoclonal antibody against human LAT1, and prognosis of patients with prostate cancer, was investigated. The intensity and score of immunohistochemical LAT1 expression of first biopsy samples were assessed using the modified Sinicrope et al. method and were found to be correlated with poor survival for the study group of 114 surgically treated patients as a whole (P = 0.0002 and 0.0270, respectively). LAT1 intensity further had a significant relationship (P = 0.0057) with prognosis in pathological T3 + T4 groups. Multivariate analysis indicated that the LAT1 intensity and score were more reliable prognostic markers, compared with the Gleason score and the Ki-67 labeling index. A relationship of the LAT1 intensity and score with prognosis could also be confirmed in 63 patients with inoperable cancer (P = 0.0070 and <0.0001, respectively). Similarly, significant differences in prognosis were confirmed in clinical T3 + T4 groups (P = 0.0091 and 0.0244, respectively). Moreover, the combination of LAT1 expression and Gleason score was found to have a more reliable correlation with prognosis. Thus, elevated LAT1 expression in prostate cancers is a novel independent biomarker of high-grade malignancy, which can be utilized together with the Gleason score, which is mainly dependent on cellular and structural atypia, to assess prognosis. [source] How Safe Is It to Transplant Organs from Deceased Donors with Primary Intracranial Malignancy?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010An Analysis of UK Registry Data Patients dying from primary intracranial malignancy are a potential source of organs for transplantation. However, a perceived risk of tumor transfer to the organ recipient has limited their use. We evaluated the risk of tumor transmission by reviewing the incidence in patients transplanted in the UK. Information from the UK Transplant Registry was combined with that from the national cancer registries of England, Wales and Northern Ireland to identify all organ donors between 1985 and 2001 inclusive with a primary intracranial malignancy and to identify the occurrence of posttransplant malignancy in the recipients of the organs transplanted. Of 11 799 organ donors in the study period, 179 were identified as having had a primary intracranial malignancy, including 33 with high-grade malignancy (24 grade IV gliomas and 9 medulloblastomas). A total of 448 recipients of 495 organs from 177 of these donors were identified. No transmission of donor intracranial malignancy occurred. Organs from patients dying from primary intracranial malignancy, including those with high-grade tumors, should be considered for transplantation and the small risk of tumor transmission should be balanced against the likely mortality for potential recipients who remain on the transplant waiting list. [source] Search for new biomarkers of gastric cancer through serial analysis of gene expression and its clinical implicationsCANCER SCIENCE, Issue 5 2004Wataru Yasui Gastric cancer is one of the most common human cancers and is the second most frequent cause of cancer-related death in the world. Serial analysis of gene expression (SAGE) is a powerful technique to allow genome-wide analysis of gene expression in a quantitative manner without prior knowledge of the gene sequences. SAGE on 5 samples of gastric cancer with different histology and clinical stages have created large SAGE libraries of gastric cancer that enable us to identify new cancer biomarkers. Commonly up-regulated genes in gastric cancer in comparison with normal gastric epithelia included CEACAM6, APOC1 and YF13H12. By comparing gene expression profiles of gastric cancers at early and advanced stages, several genes differentially expressed by tumor stage were also identified, including FUS, CDH17, COL1A1 and COL1A2, which should be novel genetic markers for high-grade malignancy. Regenerating gene type IV (REGIV) is one of the most up-regulated genes in a SAGE library of a scirrhous-type gastric cancer. In vitro studies using RegIV-transfected cells revealed that RegIV is secreted by cancer cells and inhibits apoptosis, suggesting that RegIV may serve as a novel biomarker and therapeutic target for gastric cancer. Production of RNA aptamers could be a useful approach to establish a detection system in blood. A custom-made array, named Ex-STO-MACHIP, consisting of 395 genes, including highly differentially expressed genes identified by our SAGE and other known genes related to carcinogenesis and chemosensitivity, is useful to study the molecular pathogenesis of gastric cancer and to obtain information about biological behavior and sensitivity to therapy in the clinical setting. Combined analyses of gene expression profile, genetic polymorphism and genetic instability will aid not only cancer detection, but also characterization of individual cancers and patients, leading to personalized medicine and cancer prevention. [source] | ||||||||||