Publications by authors named "B Ortega"

132 Publications

Ten-year assessment of a cancer fast-track programme to connect primary care with oncology: reducing time from initial symptoms to diagnosis and treatment initiation.

ESMO Open 2021 May 11;6(3):100148. Epub 2021 May 11.

Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain. Electronic address:

Background: Cancer is the second leading cause of mortality worldwide. Integrating different levels of care by implementing screening programmes, extending diagnostic tools and applying therapeutic advances may increase survival. We implemented a cancer fast-track programme (CFP) to shorten the time between suspected cancer symptoms, diagnosis and therapy initiation.

Patients And Methods: Descriptive data were collected from the 10 years since the CFP was implemented (2009-2019) at the Clinico-Malvarrosa Health Department in Valencia, Spain. General practitioners (GPs), an oncology coordinator and 11 specialists designed guidelines for GP patient referral to the CFP, including criteria for breast, digestive, gynaecological, lung, urological, dermatological, head and neck, and soft tissue cancers. Patients with enlarged lymph nodes and constitutional symptoms were also considered. On identifying patients with suspected cancer, GPs sent a case proposal to the oncology coordinator. If criteria were met, an appointment was quickly made with the patient. We analysed the timeline of each stage of the process.

Results: A total of 4493 suspected cancer cases were submitted to the CFP, of whom 4019 were seen by the corresponding specialist. Cancer was confirmed in 1098 (27.3%) patients: breast cancer in 33%, urological cancers in 22%, gastrointestinal cancer in 19% and lung cancer in 15%. The median time from submission to cancer testing was 11 days, and diagnosis was reached in a median of 19 days. Treatment was started at a median of 34 days from diagnosis.

Conclusions: The findings of this study show that the interval from GP patient referral to specialist testing, cancer diagnosis and start of therapy can be reduced. Implementation of the CFP enabled most patients to begin curative intended treatment, and required only minimal resources in our setting.
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http://dx.doi.org/10.1016/j.esmoop.2021.100148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136438PMC
May 2021

Nanoporous Anodic Alumina-Based Sensor for miR-99a-5p Detection as an Effective Early Breast Cancer Diagnostic Tool.

ACS Sens 2021 03 18;6(3):1022-1029. Epub 2021 Feb 18.

CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain.

Circulating microRNAs have emerged as potential diagnostic biomarkers. The deregulation of the microRNA miR-99a-5p has been previously described as an effective biomarker of early breast cancer. Herein, we present a new nanoporous anodic alumina (NAA)-based biosensor that can detect plasma miR-99a-5p with high sensitivity and selectivity. NAA pores are loaded with rhodamine B and capped with a specific oligonucleotide that is able to block cargo release until the target is present. In the presence of miR-99a-5p, the capping oligonucleotide recognizes the miR-99a-5p sequence and displaces it allowing the release of the encapsulated dye. This method is able to successfully distinguish healthy controls from breast cancer patients, even at early stages with high efficiency, showing the presented system as a promising tool for breast cancer detection.
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http://dx.doi.org/10.1021/acssensors.0c02222DOI Listing
March 2021

NOTCH signalling in ovarian cancer angiogenesis.

Ann Transl Med 2020 Dec;8(24):1705

King's College London, School of Medicine, Guy's Campus, London, UK.

The Notch signalling pathway is involved in the new vessel formation process by regulating tip and stalk cells, which are key cells in the sprout formation. This process is essential in both normal ovary and cancer angiogenesis and is regulated by Notch-VEGF crosstalk. Furthermore, Notch has been linked in ovary with stem cell maintenance and epithelial mesenchymal transition processes. Dysregulation of the Notch pathway is frequent in ovarian cancer (OC) and it has been associated with impaired survival and advanced stages or lymph node involvement. Notch also plays a role in chemoresistance to platinum. In this context, this pathway has emerged as an attractive target for precision medicine in OC. Two main targets of this pathway concentrate the clinical development of compounds blocking Notch: gamma secretase and Delta-like ligand 4. Most of the clinical trials including OC patients have been developed in phase I or phase Ib. Despite being in an early phase, both of these compounds, navicixizumab or demcizumab, two monoclonal antibodies targeting Dll4, showed promising efficacy data in platinum-resistant OC patients in recent studies. This review will focus on the mechanisms of the Notch pathway with special interest in angiogenesis regulation and the implication of Notch as a potential therapeutic target in OC.
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http://dx.doi.org/10.21037/atm-20-4497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812236PMC
December 2020

Circulating miR-30b-5p levels in plasma as a novel potential biomarker for early detection of breast cancer.

ESMO Open 2021 Feb 18;6(1):100039. Epub 2021 Jan 18.

Biomedical Research Institute INCLIVA, Valencia, Spain; Clinical Oncology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. Electronic address:

Background: Recently, microRNAs have been demonstrated to be potential non-invasive biomarkers for diagnosis, prognosis assessment or prediction of response to treatment in cancer. In this study, we evaluate the potential of miR-30b-5p as a biomarker for early diagnosis of breast cancer (BC) in tissue and plasma.

Methods: Expression of miR-30b-5p was determined in a series of 112 BC and 40 normal breast tissues. Circulating miR-30b-5p levels in plasma samples were determined in a discovery cohort of 38 BC patients and 40 healthy donors and in a validation cohort of 83 BC patients and 83 healthy volunteers. miR-30b-5p expression was measured by quantitative real-time PCR and receiver operating characteristics curve analysis was carried out.

Results: The miR-30b-5p expression was significantly lower in BC tissue than in healthy breast samples. In contrast, circulating miR-30b-5p levels were significantly higher in BC patients compared with healthy donors. Furthermore, circulating miR-30b-5p levels were significantly higher in patients with positive axillary lymph node and de novo metastatic patients. Receiver operating characteristics curve analysis demonstrated a good diagnostic potential of miR-30b-5p to detect BC even at an early stage of the disease.

Conclusion: Thus, we highlight the potential of miR-30b-5p as a non-invasive, fast, reproducible and cost-effective diagnostic biomarker of BC.
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http://dx.doi.org/10.1016/j.esmoop.2020.100039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820029PMC
February 2021

Human Stromal Cell Aggregates Concentrate Adipose Tissue Constitutive Cell Population by In Vitro DNA Quantification Analysis.

Plast Reconstr Surg 2020 12;146(6):1285-1293

From the Cancer Cell Biology Group, Institut d'Investigació Sanitària Illes Balears; Servei de Genètica, Hospital Universitari Son Espases; Institut Català d'Oncologia, Hospital Germans Trias i Pujol; Cell Pro Tech Spain; and the University of Florida College of Medicine.

Background: Regenerative cell strategies rely on stromal cell implants to attain an observable clinical outcome. However, the effective cell dose to ensure a therapeutic response remains unknown. To achieve a higher cell dose, the authors hypothesized that reducing the volume occupied by mature adipocytes in lipoaspirate will concentrate the stromal vascular fraction present in the original tissue.

Methods: Human standardized lipoaspirate (n = 6) was centrifuged (1200 g for 3 minutes) and the water phase was discarded. Mechanical disaggregation was achieved by shearing tissue through 2.4- and 1.2-mm Luer-to-Luer transfers. After a second centrifugation (800 g for 10 minutes), stromal cell aggregates were separated from the supernatant oil phase. Lipoaspirate percentage composition was determined by its constituent weights. Cell content was measured by total DNA quantification, and partial cell viability was determined by image cytometry. Tissue sections were evaluated histologically (hematoxylin and eosin and Masson trichrome stains).

Results: Stromal cell aggregates reduced the standardized lipoaspirate mass to 28.6 ± 4.2 percent. Accordingly, the cell density increased by 222.6 ± 63.3 percent (from 9.9 ± 1.4 million cells/g to 31.3 ± 6.6 million cells/g; p < 0.05). Cell viability was unaffected in stromal cell aggregates (71.3 ± 2.5 percent) compared to standardized lipoaspirate (72.2 ± 2.3 percent), and histologic analysis revealed high-density areas enriched with stromal cells (622.9 ± 145.6 percent) and extracellular matrix (871.2 ± 80.3 percent).

Conclusion: Stromal cell aggregates represent a biological agent that triplicates the cell density versus unprocessed lipoaspirate, low on oil and water fluids, and enriched extracellular matrix components.
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http://dx.doi.org/10.1097/PRS.0000000000007342DOI Listing
December 2020