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Summary:untreated patients shows little effect of adjuvant therapy in the first 4 years and only a modest statistically significant effect thereafter. 2 Thus, a trend toward a more aggressive The study was designed to determine the toxicity, feasibility, and effectiveness of high-dose cyclophosphamide approach for this subset of patients has occurred in the last years. (6 g/m 2 ), thiotepa (500 mg/m 2 ) and carboplatin (800 mg/m 2 ) (CTCb) with hematopoietic rescue as consoli-The dose intensity hypothesis has been the basis for most of these new treatment strategies. [3][4][5][6] Based on preclinical dation after standard-dose adjuvant chemotherapy treatment of primary high-risk breast cancer. From models which demonstrated a steep dose-response relationship for alkylating agents in breast cancer, 7,8 the use of October 1991 to September 1994, 40 patients with stage II or III breast cancer involving 10 or more nodes were high-dose chemotherapy (HDCT) with hemopoietic stem cell rescue has been broadly explored in selected patients treated with CTCb after six cycles of adjuvant therapy with an anthracycline-containing regimen. Bone marwith breast cancer in the last decade. To begin with, clinical trials were performed in the context of metastatic row (BM) was used as the source hematopoietic stem cell in the first 23 patients and G-CSF-mobilized periphdisease 9-11 but the availability of better support, as well as the current low mortality rates, have extended this approach eral blood progenitor cells (PBPC) in the other 17. No therapy-related deaths occurred, but three life-threatento patients with high-risk disease. The impact of this new indication for autologous blood or marrow transplantation ing complications were recorded which resolved: bilateral pulmonary hemorrhage, veno-occlusive disease of has become apparent, since 35% of all autologous transplants performed in the United States in 1994 were for the liver and pulmonary thromboembolism. PBPC result in faster hemopoietic reconstitution with signifibreast cancer. 12 Accordingly, questions as to efficacy, toxicity, and cost have beleaguered this new technology from cantly lower transfusion requirements. With a median follow-up of 35 months (23-59) actuarial event-free surthe start, and different randomized trials are currently under way. 13 Nevertheless, substantial controversy remains convival for the study patients at 3 years is 72% (CI 95%: 66-81%). Even in patients over 50-60 years, CTCb is cerning selection criteria defining the patient populations for which this therapy is the treatment of choice, in which a relatively well tolerated regimen which appears, after a median follow-up of nearly 3 years, to decrease others it remains investigational, and whether this therapy has been well enough developed for routine use in the adjurelapse frequency as compared with historical series, although a definite role of HDT in the treatment of highvant setting for high-risk patients. 14,15 Because of the above-mentioned adverse outcome with risk primary breast c...

Since the advent of the new proteomics era more than a decade ago, large-scale studies of protein profiling have been used to identify distinctive molecular signatures in a wide array of biological systems, spanning areas of basic biological research, clinical diagnostics, and biomarker discovery directed toward therapeutic applications. Recent advances in protein separation and identification techniques have significantly improved proteomic approaches, leading to enhancement of the depth and breadth of proteome coverage.Proteomic signatures, specific for multiple diseases, including cancer and pre-invasive lesions, are emerging. This article combines, in a simple manner, relevant proteomic and OMICS clues used in the discovery and development of diagnostic and prognostic biomarkers that are applicable to all clinical fields, thus helping to improve applications of clinical proteomic strategies for translational medicine research.

Mass Spectrometry (MS)‐based phosphoproteomics tools are crucial for understanding the structure and dynamics of signaling networks. Approaches such as affinity purification followed by MS have also been used to elucidate relevant biological questions in health and disease. The study of proteomes and phosphoproteomes as linked systems, rather than research studies of individual proteins, are necessary to understand the functions of phosphorylated and un‐phosphorylated proteins under spatial and temporal conditions. Phosphoproteome studies also facilitate drug target protein identification which may be clinically useful in the near future. Here, we provide an overview of general principles of signaling pathways versus phosphorylation. Likewise, we detail chemical phosphoproteomic tools, including pros and cons with examples where these methods have been applied. In addition, basic clues of electrospray ionization and collision induced dissociation fragmentation are detailed in a simple manner for successful phosphoproteomic clinical studies.

The activation of signaling cascades in response to extracellular and intracellular stimuli to control cell growth, proliferation and survival, is orchestrated by protein kinases via phosphorylation. A critical issue is the study of the mechanisms of cancer cells for the development of more effective drugs. With the application of the new proteomic technologies, together with the advancement in the sequencing of the human proteome, patients will therefore be benefited by the discovery of novel therapeutic and/or diagnostic protein targets. Furthermore, the advances in proteomic approaches and the Human Proteome Organization (HUPO) have opened a new door which is helpful in the identification of patients at risk and towards improving current therapies. Modification of the signaling-networks via mutations or abnormal protein expression underlies the cause or consequence of many diseases including cancer. Resulting data is used to reveal connections between genes proteins and compounds and the related molecular pathways for underlining disease states. As a delegate of HUPO, for human proteome on children assays and studies, we, at Hospital Universitario Niño Jesús, are seeking to support the human proteome in this context. Clinical goals have to be clearly established and proteomics experts have to set up the appropriate proteomic strategy, which coupled to bioinformatics will make it possible to achieve new therapies for patients with poor prognosis. We envision to combine our up-coming data to the HUPO organization in order to support international efforts to advance the cure of cancer disease.