Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer

Prostate cancer is the second most diagnosed cancer in males in the world. Plasma quantification of prostate-specific antigen substantially improved the early detection of prostate cancer, but still lacks the required specificity. Clinical management of prostate cancer needs advances in the development of new non-invasive biomarkers, ameliorating current diagnosis and prognosis and guiding therapeutic decisions. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. These miRNAs are expressed in the cells and are also present in cell-derived extracellular vesicles such as exosomes. Exosomes have been shown to act as mediators for cell to cell communication because of the regulatory functions of their content. High levels of exosomes are found in several body fluids from cancer patients and could be a potential source of non-invasive biomarkers. In this review, we summarize the diagnostic and prognostic utility of exosomal miRNAs in prostate cancer (AU)

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Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer.

Prostate cancer is the second most diagnosed cancer in males in the world. Plasma quantification of prostate-specific antigen substantially improved the early detection of prostate cancer, but still lacks the required specificity. Clinical management of prostate cancer needs advances in the development of new non-invasive biomarkers, ameliorating current diagnosis and prognosis and guiding therapeutic decisions. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. These miRNAs are expressed in the cells and are also present in cell-derived extracellular vesicles such as exosomes. Exosomes have been shown to act as mediators for cell to cell communication because of the regulatory functions of their content. High levels of exosomes are found in several body fluids from cancer patients and could be a potential source of non-invasive biomarkers. In this review, we summarize the diagnostic and prognostic utility of exosomal miRNAs in prostate cancer.

A safer disposal of hazardous phosphate coating sludge by formation of an amorphous calcium phosphate matrix.

Phosphate coating hazardous wastes originated from the automotive industry were efficiently encapsulated by an acid-base reaction between phosphates present in the sludge and calcium aluminate cement, yielding very inert and stable monolithic blocks of amorphous calcium phosphate (ACP). Two different compositions of industrial sludge were characterized and loaded in ratios ranging from 10 to 50 wt.%. Setting times and compressive strengths were recorded to establish the feasibility of this method to achieve a good handling and a safe landfilling of these samples. Short solidification periods were found and leaching tests showed an excellent retention for toxic metals (Zn, Ni, Cu, Cr and Mn) and for organic matter. Retentions over 99.9% for Zn and Mn were observed even for loadings as high as 50 wt.% of the wastes. The formation of ACP phase of low porosity and high stability accounted for the effective immobilization of the hazardous components of the wastes.

Treatment of toxic metal aqueous solutions: encapsulation in a phosphate-calcium aluminate matrix.

Polyphosphate-modified calcium aluminate cement matrices were prepared by using aqueous solutions polluted with toxic metals as mixing water to obtain waste-containing solid blocks with improved management and disposal. Synthetically contaminated waters containing either Pb or Cu or Zn were incorporated into phosphoaluminate cement mortars and the effects of the metal's presence on setting time and mechanical performance were assessed. Sorption and leaching tests were also executed and both retention and release patterns were investigated. For all three metals, high uptake capacities as well as percentages of retention larger than 99.9% were measured. Both Pb and Cu were seen to be largely compatible with this cementitious matrix, rendering the obtained blocks suitable for landfilling or for building purposes. However, Zn spoilt the compressive strength values because of its reaction with hydrogen phosphate anions, hindering the development of the binding matrix.

Solidification/stabilization of toxic metals in calcium aluminate cement matrices.

The ability of calcium aluminate cement (CAC) to encapsulate toxic metals (Pb, Zn and Cu) was assessed under two curing conditions. Changes in the consistency and in the setting time were found upon the addition of the nitrates of the target metals. Both Pb and Cu caused a delay in CAC hydration, while Zn accelerated the stiffening of the mortar. Compressive strengths of the metal-doped mortars, when initially cured at 60 °C/100% RH, were comparable with that of the free-metal mortar. Three different pore size distribution patterns were identified and related to the compounds identified by XRD and SEM. Sorbent capacities of CAC for the toxic metals were excellent: a total uptake was achieved for up to 3 wt.% loading of the three metals. In this way, CAC mortars were perfectly able to encapsulate the toxic metals, allowing the use of CAC for waste management as proved by the leaching tests.

The prognostic value of hTERT expression levels in advanced-stage colorectal cancer patients: a comparison between tissue and serum expression

AIM: Telomeres are regions of highly repetitive, non-coding DNA located at the termini of chromosomes whose principal function is to maintain the structural stability of these ends. In 90% of human tumours, telomere length is maintained by the expression and activation of telomerase reverse transcriptase. Various studies have demonstrated an increase in telomerase activity in tumour tissue, which suggests its possible prognostic value. The main objective of our study was to study the prognostic value of the expression level of telomerase catalytic component (hTERT) in patients with colorectal cancer (CRC). METHODS: We analysed the prognostic value of the ratio of telomerase expression in tumour tissue to telomerase expression in the adjacent healthy mucosa and the prognostic value of the expression level of hTERT in the serum of patients diagnosed with CRC. As secondary objectives of the study, we (1) analysed the correlation between telomerase expression in the serum and that in the tumour tissue and (2) analysed the relationship between telomerase expression and different clinical parameters. RESULTS: Peripheral blood and tissue samples taken from 48 patients with CRC were analysed. No significant differences were observed in disease-free survival (DFS) or overall survival time (OST) between the groups of patients categorised based on the ratio of telomerase expression between tumour tissue and healthy tissue. The correlation index (Pearson's coefficient) between telomerase levels in the serum and those in tissue was 0.32. Our study of the relationship between telomerase levels in the serum and different clinical variables, such as tumour size, ganglion affectation, preoperative carcinoembryonic antigen levels and stage, revealed a higher telomerase expression level in patients with stage IV CRC. There was no significant association between telomerase expression in tumour tissue and the clinical parameters analysed. CONCLUSIONS: The results obtained in our study do not allow us to propose that the level of telomerase expression be used as a prognostic factor in colorectal cancer. Thus, we cannot consider telomerase expression in the serum as a surrogate marker of its expression in tumour tissue (AU)

Phase II clinical trial with gemcitabine and paclitaxel sequential monotherapy as first-line treatment for advanced non-small-cell lung cancer (SLCG 01-04)

BACKGROUND: In advanced-stage (IIIB or IV) non-small-cell lung cancer (NSCLC), combination chemotherapy has demonstrated response rates of 20% and a 1-year survival rate of 30%. We conducted a multicentre, open-label, nonrandomised phase II trial to determine the efficacy and tolerability of sequential monotherapy with gemcitabine followed by paclitaxel in chemotherapy-naïve patients with advanced NSCLC. MATERIALS AND METHODS: Between December 2002 and July 2004, the Spanish Lung Cancer Group (SLCG) conducted a study in which 34 patients with advanced (stage IIIB or IV) NSCLC received 1200 mg/m(2) of i.v. gemcitabine on days 1, 8 and 15 of each 28-day cycle for a total of 3 cycles followed by 100 mg/m(2) of weekly i.v. paclitaxel for a maximum of 8 weeks. If objective response or stable disease was achieved, 70 mg/m(2) of weekly i.v. paclitaxel was maintained until disease progression was evident or toxic effects were intolerable. Lung Cancer Symptom Scale (LCSS) analysis was performed. Baseline levels of serum VEGF, EGFR, telomerase reverse transcriptase (hTERT) and K-ras mutations were analysed. The primary endpoint was the objective response rate. RESULTS: The median age of the 34 patients who were enrolled was 67 years (range 46-77), but later 8 patients were excluded; 78.8% were men, 81.8% had performance status 1 and also 81.8% had metastatic disease at diagnosis. The objective response rate was 28% (95% CI, 14.2-47.8); the median overall survival was 7.2 months (95% CI, 2.1-12.3) and the median time to progression (TTP) was 3.1 months (95% CI, 2.5-5.3). Grade 3 or 4 drug-related haematological toxicities were observed in 6 patients. Patients with lower baseline serum VEGF levels had significantly longer survival. CONCLUSIONS: Sequential therapy with gemcitabine followed by paclitaxel was well tolerated with a low proportion of grade 3 or 4 adverse events, the absence of unexpected toxicity and with an improvement in quality of life. Unfortunately, the response rate did not meet the minimally required rate of 20% and the study was prematurely closed. VEGF was identified as a poor prognostic factor for TTP and survival (AU)

Oncology outside hospital: a new experience for the benefit of longer survivors

In May 2007, the Consorcio Hospital General Universitario de Valencia created the position of "Liaison Oncologist". The holder of this position is responsible for coordinating specialised and primary hospital care in the geographic area of Valencia known as Health Care Department 9 to reduce the waiting time between cancer diagnosis and treatment. In this article we describe the implementation of the innovative proposal of the Liaison Oncologist's Consultation Clinic, which, apart from speeding up and directing diagnostic processes, facilitates access to treatment, prevents duplication of consultations and exploratory procedures by establishing therapeutic plans (preferential channels), gives continuity to diagnostic and therapeutic mechanisms, and permits active follow-up of patients who have finished treatment. An analysis of the results obtained shows that the clinic has allowed us to integrate the various aspects of medical oncology into one system and make it available to patients and primary and specialised care professionals. This system provides the patient with the highest quality of integrated health care, ensures the availability of continued health care to long-term survivors and establishes preferential channels between primary care and specialised cancer care to achieve a quick diagnosis (AU)

Can the Spanish care system assume the new costs of medications against cancer?

Cancer is a high incidence disease, forcing healthcare systems to assign a significant amount of resources to its treatment. New developments have arisen recently: development of new agents that act at specific steps of cellular differentiation and proliferation and identification of predictive genetic markers which allow sub-groups of patients that will benefit from these agents, alone or in combination with chemotherapy, to be targeted. The majority of new drugs coming to the market combine greater clinical benefit and higher costs. Constraints on healthcare budgets worldwide make it necessary to rationalise the expense by prioritising allocation of available resources to the most efficient interventions, so that the best possible clinical result can be obtained at a reasonable cost and with the best quality of life for the patient. Economic evaluation studies represent the only tool available to scientifically determine the cost-effectiveness of new treatments and the budgetary impact of their introduction to the therapeutic arsenal available for the treatment of cancer (AU)

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Venous thromboembolic disease in cancer. Optimisation of the use of antithrombotic agents.

Venous thromoboembolism is one of the most common complications in cancer patients and may have serious consequences. At present, most clinical oncologists report using thromboprophylaxis in less than 5% of patients. One of the possible reasons for this limited use is the lack of oncology specific guidelines. In effect, while there are excellent guidelines for optimising the use of antithrombotic agents to prevent and treat thromboembolism, they must be adapted to the concrete context of cancer patients. The present review explores how different situations affect cancer patients and their risk of developing venous thromboembolism (VTE), and evaluates the situations in which antithrombotic agents should be administered to treat and prevent VTE.

Venous thromboembolic disease in cancer. Optimisation of the use of antithrombotic agents

Venous thromoboembolism is one of the most common complications in cancer patients and may have serious consequences. At present, most clinical oncologists report using thromboprophylaxis in less than 5% of patients. One of the possible reasons for this limited use is the lack of oncology specific guidelines. In effect, while there are excellent guidelines for optimising the use of antithrombotic agents to prevent and treat thromboembolism, they must be adapted to the concrete context of cancer patients. The present review explores how different situations affect cancer patients and their risk of developing venous thromboembolism (VTE), and evaluates the situations in which antithrombotic agents should be administered to treat and prevent VTE (AU)