Research team:

Dr. Melissa Bardbury (Principal researcher)

Dr. Antonio Gil-Moreno (Principal researcher)

Dra. Anna Santamaría (Stable collaborator)

Dr. Eva Coll (PhD student)

Dr. Carlos López (PhD student)

Dr. Melek Denizli (Technician)

Dr. José Luís Sánchez Iglesias (Clinical associated investigator)

Dr. Armando Reques (Clinical associated investigator)

Dr. Assumpció Pérez-Benavente (Clinical associated investigator)

Dr. Vicente Bebia Conesa (Clinical associated investigator)

Dr. Natalia Rodríguez Gómez-Hidalgo (Clinical associated investigator)

Dr. Javier de la Torre Fernández de Vega (Clinical associated investigator)

Research focus

PERIOPERATIVE IMMUNOMODULATION IN OVARIAN CANCER

Surgery for advanced ovarian cancer is a stressful stimulus that results in a pro-catabolic hormonal and cytokine environment, which significantly impacts metabolism. This metabolic response is accompanied by immune system impairment, increasing the risk of post-operative complications. In this research line the group is working in a multidisplinary project within the ERAS® program at the Vall d’Hebron Hospital for the: 

Identification of inflammatory markers predicting improved recovery after surgery within an ERAS® protocol.

MOLECULAR DIAGNOSTICS AND PREDICTION OF TREATMENT RESPONSE IN OVARIAN CANCER

Ovarian cancer remains the leading cause of death from gynecological malignancies due to its late diagnosis and high recurrence rates following treatment. There is a need to improve the early detection of the disease and identify predictive markers of treatment response. These diagnostic and predictive markers are being identified in proximal body fluids and patient-tissue samples. In this research line, the group has 3 ongoing projects:

Proteomic biomarkers for an improved diagnosis in uterine aspirates and pap-smears.

Proteomic biomarkers for the prediction of treatment response.

SalivOmiX: A salivary miRNA-based test for ovarian cancer early diagnosis.

Research team:

Dr. Antonio Gil-Moreno (Principal researcher)

Dr. Assumpció Pérez-Benavente (Clinical associated investigator)

Dr. José Lúís Sánchez Iglesias (Clinical associated investigator)

Dra. Silvia Cabrera (Clinical associated investigator)

Dr. Vicente Bebia Conesa (Clinical associated investigator)

Dr. Natalia Rodríguez Gómez-Hidalgo (Clinical associated investigator)

Dr. Javier de la Torre Fernández de Vega (Clinical associated investigator)

Dr. José Luís Poza Barrasús (Clinical associated investigator)

Dr. Sabina Salicrú Riera (Clinical associated investigator)

Dr. Laura Mañalich Barrachina (Clinical associated investigator)

Dr. Montse Cubo Albert (Clinical associated investigator)

Dr. Cristina Centeno Mediavilla (Clinical associated investigator)

Dr. Melissa Bradbury (Clinical associated investigator)

Dr. Sonia Monreal (Clinical associated investigator)

Dr. Angel García (Clinical associated investigator)

Dr. Armando Reques (Clinical associated investigator)

Dr. Elena Suárez (Clinical associated investigator)

Dr. Mireia Armengol (Clinical associated investigator/resident)

Dra. Eva Colás (Translational associated researcher)

Dr. Melek Denizli (Technician)

Research focus. Clinical Research Lines

CLINICAL ENDOMETRIAL CANCER RESEARCH

- Prospective, randomized study: STELLA1-2 Trial: Transperitoneal vs. Extraperitoneal Approach for Laparoscopic Staging of Endometrial/Ovarian Cancer. ClinicalTrials.gov Identifier: NCT01810874.

- Implementation of radioguided surgery for clinically occult lesions (ROLL) in abdominal recurrences of gynecological tumors.

- MULTISENT study: Ambiespective multicenter study of sentinel node biopsy in initial endometrial cancer.

- Concordance study between morphological techniques and OSNA (one-step nucleic cid amplification) for the detection of lymph node metastases in endometrial carcinoma.

- Preoperative staging of endometrial carcinoma by ultrasound 2D and 3D.

CLINICAL OVARIAN CANCER RESEARCH

- Prospective study: Postoperatory Recovery in Advanced Ovarian Cancer, Fast-Track Protocol vs. Classical Management (PROFAST). ClinicalTrials.gov Identifier: NCT02172638.

- EDMOCS study in ovarian cancer.

- SIMACEO study: Current Situation of the Management of Epithelial Cancer of the Ovary in initial stages in Spain.

CLINICAL CERVICAL CANCER RESEARCH

- Prospective study of validation of sentinel lymph node detection technique in early cervical cancer (FIGO 2018 stages IA2-IB1-IB2-IIA1).

- Collaborating center in the RACC Trial study (PI: Karolynska Hospital, Sweden): International, Prospective, Randomized comparative study of robotic versus laparotomic radical hysterectomy approach in early cervical cancer.

- Validation of robotic assisted and laparoscopic aortic extraperitoneal lymphadenectomy in recurrences of gynaecologic malignancies.

- Preoperative staging of carcinoma of the uterine cervix by ultrasound 2D and 3D.

CLINICAL RESEARCH IN BENIGN GYNECOLOGY

- Prospective study: Multicentric Comparative Randomized Study of the Single-incision Sling Ajust® Versus Suburethral Transobturator Slings. ClinicalTrials.gov Identifier: NCT01699425

- “A 3 Years Naturalistic Cohort Survey Of Altis® Single Incision Sling System For Female Stress Urinary Incontinence. A post-marketing and multicenter prospective observational cohort study in subjects with female stress urinary incontinence”.

- "Non-interventional study to evaluate quality of life, satisfaction with treatment, use of resources and persistence in treatment in patients with overactive bladder (OAB) who were prescribed Betmiga".

- “Comparative study of polyvinylidene fluoride and polypropylene suburethral-slings in the treatment of female stress urinary incontinence.”

- “Microarray analysis of differentially expressed genes in samples from patients with pelvic organ prolapse.”

Estudio EME: “Estudio epidemiológico sobre la miomatosis uterina en España”.

CLINICAL RESEARCH: MISCELLANEOUS

Prospective study of validation of sentinel lymph node detection technique in early vulvar cancer (early stages FIGO 2009)

- Prospective study of quality of life in patients with BRCA1-2 after risk-reducing adnexectomy.

- Prospective study of quality of life in patients with BRCA1-2 after risk-reducing mastectomy.

- Early detection of preneoplastic tubal lesions to delay ovarian cancer risk-reducing surgery in patients with BRCA1/2 mutations.

- Prospective, multicenter study for the evaluation of the intraoperative HPV test.

- INCIP Study: Cancer in pregnancy

- Randomized, open, multicentric, parallel group and control group clinical trial to evaluate the effect of PAPILOCARE® in the normalization of cytological alterations of the cervix caused by HPV (PALOMA II Clinical Trial).

- Cervical epithelium methylation as a risk marker of progression to HSIL in women with normal cytology and positive HPV.

- Conservative management of high-risk cervical intraepithelial lesions.

- Utility of DySIS® in the diagnosis and management of intraepithelial lesions of the lower genital tract.

- Breast Cancer During Pregnancy (BRCAPRE). ClinicalTrials.gov Identifier: NCT02102282.

Group Leaders

Jaume Reventós

Joan Morote

Andreas Doll

Principal Investigators

Jaume Reventós (MD, PhD)

Joan Morote (MD, PhD)

Andreas Doll (PhD)

Maite Quiles (PhD)

Maria Antònia Arbós (MD, PhD)

Research Team

Marta García (Graduate Student)

Marina Rigau (Graduate Student)

Jacques Planas (Clinical Associated Investigator)

Enrique Trilla (Clinical Associated Investigator)

Carlos Raventós (Clinical Associated Investigator)

José Placer (Clinical Associated Investigator)

Carlos Salvador (Resident)

Jordi Ropero (Resident)

Marta Alué (Resident)

María Carmen Mir (Resident)

Luis Castro (Resident)

Geisy Delgado (Resident)

Juan M. Bastarós (Resident)

Research Focus

Our overall goal focuses several aspects of translational urology mainly based on the knowledge of the molecular bases of prostate cancer, in particular, but also on the role of infl ammatory mechanisms as critical regulators of tumor progression. Our central hypothesis is that a deeper understanding of these pathways will advance the development of preventive treatment strategies.

Research Lines in Prostate Cancer (PC)

Development of non-invasive methods for the early detection of PC in biological fluids
We have determined the specific, differential proteomic profi les to be found in the urine of patients with PC, as compared to age matched controls, with the ultimate goal of settling on a non-invasive diagnostic tool using urine that could help to circumvent the low specifi city of the currentlyused PSA serum measurements. We use liquid chromatography, mass spectrometry and triple quadrupole mass spectrometry (LC/MSMS SRM). The Selected Reaction Monitoring technique (SRM) is an emerging technology that ideally complements the discovery capabilities of shotgun strategies through its unique potential for the reliable quantifi cation of low abundance analytes in complex mixtures, such as urine samples. Using this technique we quantify and detect diff erent selected proteins with high sensitivity and a good chromatographic separation within the complex biological samples. The final goal of this research is the establishment of a reliable diagnostic test, which can be used in hospitals and outpatient routines.

Identification of the molecular markers of bone metastases in prostate cancer

We have developed humanized animal models for metastatic prostate cancer able to mimic the human dissemination of PC cells to bones. We use immunocompromised mice transplanted with human bone. Human prostate cancer cells, which over-express luciferase, are injected, allowing metastasis detection and the continued monitoring of the living animals. This permits the identifi cation of bone metastasis markers, patients with a high risk of recurrence and could defi ne new therapeutic targets that will act to block bone lesions through conventional therapies


Development of improved bone metastasis animal models, very close to the clinics, in order to monitor the process of in vivo metastasis

We use an animal model of immunocompromised mice with a transplantation of human bone fragments. Subsequently, human PCa cell lines, over-expressing luciferase, are injected. This allows the detection and monitoring of metastasis in the living animal, since the implanted bone fragments maintain their human microenvironment.

Identification of the molecules responsible for the formation of human bone metastasis

By analyzing the changes in protein expression levels by proteomics in the metastases obtained from this animal model, we examine whether

the reinjection of bone metastasis cells aff ects the specifi city or phenotype, due to reprogramming. We attempt to identify the factors that attract human prostate cancer cells to human bone and the mechanisms that are involved in the process of metastasis. This is accomplished by proteomics, using a fl uorescence-based differential gel electrophoresis (DIGE) with mass spectrometry (MALDI / TOF), as well as isotope-based techniques (iTRAC etc.) and LC-MS/ MS with SRM.

Efficacy of new adjuvant therapies for PC bone metastasis

We use intra-tibial injection of prostate cancer cells overexpressing luciferase in immunocompromised balb/c nude mice, a straightforward method to induce local growth in bone marrow. This Bioluminescent Imaging (BLI)- based metastasis model allows us a regular monitoring of the development and progression of experimental bone metastases in living animals with high sensitivity. Fewer laboratory animals are needed as due to the noninvasive nature of the methods repetitive measurements can be taken from the same animal, which also increases the reliability of observed eff ects. This approach will enable us to include the micro-environmental growth support system of the bone for the treatment of metastatic disease.

Extracellular matrix and infl ammatory mechanisms regulated by prostate cancer-associated fibroblasts

We are interested in understanding extracellular matrix and inflammatory mechanisms regulated by cancer-associated fi broblasts (CAFs) as

promoting forces for prostate cancer progression. Cancer-associated fibroblasts support tumorigenesis by stimulating angiogenesis, cancer

cell proliferation, invasion and tumor-enhancing infl ammation. Using primary cell cultures, we have learned that prostate CAFs

display signifi cant phenotypic and transcriptional diff erences from their normal associated fi broblast (NAF) counterparts:

i) an invasive and migratory phenotype,

ii) expression of epithelial-mesenchymal transition genes and

iii) enhanced expression of inflammatory molecules.

Currently we are studying the differential response of the monocytic cell line THP1 in front of CAFs/ NAFs (cell-cell adhesion, chemotaxis, gene and protein expression, matrix metalloproteinase activation).

Molecular analysis of “proliferative inflammatory atrophy” (PIA) as a premalignant condition in prostate cancer development

We also focus our research on the potential importance of chronic inflammatory microenvironments as premalignant condition in prostate cancer development. Currently we are studying a common lesion, often associated with infl ammation, termed “proliferative inflammatory atrophy” (PIA), which has been postulated to represent an intermediate step between normal tissue and cancer. It may, therefore, serve as a risk factor lesion for prostate cancer. Using microdissection and microarray technology we have performed paired comparative analysis of gene expression in the following prostatic tissues: benign, PIA, high grade prostatic intraepithelial neoplasia (HGPIN) and cancer lesions. Our objective is to test whether:

i) our data support the notion that PIA may be considered a premalignant lesion, and

ii) we can detect and characterize common transcriptionally altered pathways among these pathologies.

These studies have implications for prevention and chemoprevention of prostate cancer.


Decrease of bone mass during androgen deprivation in prostate cancer

Decrease of plasmatic levels of testosterone produced by androgen deprivation indirectly alters the mineral bone metabolism and produces loss of bone mass and there is increased the risk of fractures and mortality. This research line contains studies of prevalence of osteoporosis and osteopenia, prediction of the pace of bone mass loss, study of the molecular mediators, specifi cs diagnosis methods and prevention.

Dyslipemia and metabolic syndrome during androgen deprivation in prostate cancer

Cardiovascular mortality is the leading cause of death in patients with prostate cancer and it is believed that androgen deprivation is the intermediate reason. This research line includes studies of metabolic syndrome prevalence and dyslipemia as the most frequent cause of cardiovascular mortality, molecular mediators analysis, early diagnosis methods of cardiovascular risk and prevention.

Cognitive alterations during androgen deprivation in prostate cancer

Androgen suppression in prostate cancer patients produces cognitive alterations that are not well studied despite being very important for quality of life. The purpose of this research line is to study the cognitive alteration profi le that produces androgen deprivation, the mediators who generate these alterations at central level, early diagnosis and possible forms of prevention.

High grade intraepithelial neoplasia and prostate cancer

High grade intraepithelial neoplasia is preneoplasics prostate cancer damage. Nevertheless, it is unknown the molecular mechanisms who define his neoplasic transformation or his persistence as high grade intraepithelial neoplasia isolated. High grade intraepithelial neoplasia detection in a prostatic biopsy entails a repeat biopsy strategy that has not yet been clearly established. This research line integrates the analysis of molecular predictors of neoplasic transformation (genomics and proteomics), the analysis of metabolic image (RNM and spectroscopy) and possible prevention mechanisms of prostate cancer chemoprofilaxis.

Research Lines in Kidney Diseases

Pneumoperitoneum impact of laparoscopic surgery on renal function

Analysis of molecular mechanisms of renal oncogeny