Podcasts about background cancer

Background: Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different tumor types may help to guide selection of targeted therapy in translational research. Concise grouping of tumor types in cancer maps according to their molecular profile may further be helpful for the development of new therapeutic modalities or open new avenues for already established therapies. Methods: Complete available human tumor data of the Stanford Microarray Database was downloaded and filtered for relevance, adequacy and reliability. A total of 649 tumor samples from more than 1400 experiments and 58 different tissues were analyzed. Next, a method to score deregulation of KEGG pathway maps in different tumor entities was established, which was then used to convert hundreds of gene expression profiles into corresponding tumor-specific pathway activity profiles. Based on the latter, we defined a measure for functional similarity between tumor entities, which yielded to phylogeny of tumors. Results: We provide a comprehensive, easy-to-interpret functional cancer map that characterizes tumor types with respect to their biological and functional behavior. Consistently, multiple pathways commonly associated with tumor progression were revealed as common features in the majority of the tumors. However, several pathways previously not linked to carcinogenesis were identified in multiple cancers suggesting an essential role of these pathways in cancer biology. Among these pathways were `ECM-receptor interaction', `Complement and Coagulation cascades', and `PPAR signaling pathway'. Conclusion: The functional cancer map provides a systematic view on molecular similarities across different cancers by comparing tumors on the level of pathway activity. This work resulted in identification of novel superimposed functional pathways potentially linked to cancer biology. Therefore, our work may serve as a starting point for rationalizing combination of tumor therapeutics as well as for expanding the application of well-established targeted tumor therapies.

Background: Cancer antigen 125 (CA125) is the best known single tumor marker for ovarian cancer (OC). We investigated whether the additional information of the human epididymis protein 4 (HE4) improves diagnostic accuracy. Methods: We retrospectively analyzed preoperative sera of 109 healthy women, 285 patients with benign ovarian masses (cystadenoma: n = 78, leimyoma: n = 66, endometriosis: n = 52, functional ovarian cysts: n = 79, other: n = 10), 16 low malignant potential (LMP) ovarian tumors and 125 OC (stage 1: 22, II: 15, III: 78, IV: 10). CA 125 was analyzed using the ARCHITECT system, HE4 using the ARCHITECT(a) system and EIA(e) technology additionally. Results: The lowest concentrations of CA125 and HE4 were observed in healthy individuals, followed by patients with benign adnexal masses and patients with LMP tumors and OC. The area under the curve (AUC) for the differential diagnosis of adnexal masses of CA 125 alone was not significantly different to HE4 alone in premenopausal (CA 125: 86.7, HE4(a): 82.6, HE4(e): 81.6% p > 0.05) but significantly different in postmenopausal {[}CA125: 93.4 vs. HE4(a): 88.3 p = 0.023 and vs. HE4(e): 87.8% p=0.012] patients. For stage I OC, HE4 as a single marker was superior to CA 125, which was the best single marker in stage H-IV. The combination of CA 125 and HE4 using risk of malignancy algorithm (ROMA) gained the highest sensitivity at 95% specificity for the differential diagnosis of adnexal masses {[}CA 125: 70.9, HE4(a): 67.4, HE4(e): 66.0, ROMA(a): 76.6 and ROMA(e): 74.5%], especially in stage I OC {[}CA 125: 27.3, HE4(a): 40.9, HE4(e): 40.9, ROMA(a): 45.5 and ROMA(e): 45.5%]. Conclusions: CA 125 is still the best single marker in the diagnosis of OC. HE4 alone and even more the combined analysis of CA 125 and HE4 using ROMA improve the diagnostic accuracy of adnexal masses, especially in early OC.

Background: Cancer antigen CA15-3 antigen is known as a valuable marker for the management of breast cancer. Methods: The analytical and clinical performance of the Access' BR Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA15-3 on the Elecsys(R) System (Roche Diagnostics). Results: Total imprecision (%CV) of the BR Monitor ranged between 5.5% and 11.7%, and inter-laboratory reproducibility between 3.4% and 5.1%. Linearity upon dilution showed a mean recovery of 98.5% (SD+/-9.1%). Endogenous interferents had no influence on BR Monitor levels (mean recoveries: hemoglobin 112%, bilirubin 111%, triglycerides 108%). There was no high-dose hook effect up to 13,540 kU/L. Clinical performance investigated in sera from 1811 individuals showed a general correlation between the Access BR Monitor and Elecsys CA15-3 (R = 0.797), with a slope of 1.383. CA15-3 serum levels, as measured by the BR Monitor, were low in healthy individuals (n = 267, median = 11.9 kU/L, 95th percentile = 23.5 kU/L), higher in individuals with various benign diseases (n = 549, medians = 11.3-15.6 kU/L, 95th percentiles = 21.6-54.6 kU/L) and even higher in individuals suffering from various cancers (n = 995, medians = 11.2-22.8 kU/L, 95th percentiles = 30.0-429.7 kU/L). Best diagnostic accuracy for cancer detection against the relevant benign control group by the BR Monitor was found for locoregional and metastatic breast cancer, as well as for ovarian cancer {[}area under the curve (AUC) 0.619, 0.897 and 0.774]. Results for the reference CA15-3 assay were comparable (AUC 0.611, 0.887 and 0.818). Conclusions: The Access BR Monitor provides accurate methodological characteristics and demonstrates an analytical and clinical correlation with Elecsys CA15-3. Best diagnostic accuracy for the BR Monitor was found in breast and ovarian cancer. Our results also suggest a clinical value of the BR Monitor in other cancers.

Background: Cancer antigen CA125 is known as a valuable marker for the management of ovarian cancer. Methods: The analytical and clinical performance of the Access OV Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA125 on the Elecsys System (Roche Diagnostics). Results: Total imprecision (%CV) of the OV Monitor ranged between 3.1% and 8.8%, and inter-laboratory reproducibility between 4.7% and 5.0%. Linearity upon dilution showed a mean recovery of 100% (SD+8.1%). Endogenous interferents had no influence on OV Monitor levels (mean recoveries: hemoglobin 107%, bilirubin 103%, triglycericles 103%). There was no high-dose hook effect up to 27,193 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access OV Monitor and Elecsys CA125 (R = 0.982, slope = 0.921, intercept = + 1.951). OV Monitor serum levels were low in healthy individuals (n = 267, median = 9.7 kU/L, 95th percentile = 30.8 kU/L), higher in individuals with various benign diseases (n = 549, medians = 10.9-16.4 kU/L, 95th percentiles = 44.2-355 kU/L) and even higher in individuals suffering from various cancers (n = 995, medians= 12.4-445 kU/L; 95th percentiles = 53.4-4664 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the OV Monitor was found for ovarian cancer {[}area under the curve (AUC) 0.898]. Results for the reference CA125 assay were comparable (AUC 0.899). Conclusions: The Access OV Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with Elecsys CA125. The best diagnostic accuracy for the OV Monitor was found in ovarian cancer. Our results also suggest a clinical value of the OV Monitor in other cancers.