Researchers from the University of Granada have developed a new, quick and economic method that allows to determine if a child aged 2-4 suffers from silent celiac disease (the disease that goes unnoticed for the doctor because it presents minor symptoms, imperceptible even for the patient)

Researchers from the University of Granada (UGR) have developed a new, simple and non invasive method which allows to determine whether a child aged 2-4 suffers from celiac disease or not without the necessity of a blood extraction.

Moreover, this method doesn’t require experienced personnel (although it has to be interpreted by health professionals), is quick (10 minutes), economic (10-12 euros per device) and, most important of all in the case of infant population, this method is less invasive than a blood extraction.

This work has been carried out by Mª Vega Almazán de Bobadilla, researcher at the UGR department of Pediatrics, and lead by José Maldonado Lozano. Part of their results have been published in the Pediatric Research magazine.

As the author, pediatrician at the Health Center in Maracena (Granada, Spain), explains, “the idea of carrying out this research came from the need of responding to a question that I have considered when giving daily clinical care: is there any silent prevalence of the celiac disease in our field of specialization?”.

Silent celiac disease

Silent celiac disease is that which goes unnoticed to the eyes of the doctor because it presents minor symptoms, imperceptible even for the patient. Celiac disease is a systemic disease caused by a permanent intolerance to gluten (which can be found in wheat, barley and rye), and it affects people with genetic predisposition. The symptoms are intestinal (intestinal malabsorption, abdominal distension, diarrhea, abdominal pain, etc.) and extra-digestive (skin problems, joint pain, cephalalgia, etc.).

Nowadays, in order to diagnose celiac disease, three things are required: clinical symptomatology, the assessment of celiac disease antibodies present in blood, and a compatible histological study via intestinal biopsy.

The goal of the research carried out by the University of Granada was to assess the prevalence of the silent celiac disease among children aged 2-4. For that purpose, the researchers used new devices which allowed to detect the disease markers (auto-antibodies) present in the patient’s capillary blood.

“A puncture in the finger is enough to take a little drop of blood, which is then put in the device and, in case the subject suffers from the disease, a pink line will appear in the strip (just like in pregnancy tests). Said pink line means that there are auto-antibodies characteristic to the celiac disease present in blood”.

A study carried out with 198 children

A positive outcome of the test will require further confirmation via blood extraction and assessment of the disease antibodies via other methods, but a negative outcome will allow to dismiss, with certainty, being affected by the disease. As we have proven during our research, a negative outcome in the strip lowered the probability of suffering from celiac disease to zero, given its high negative predictive value”.

This UGR research allowed to detect 6 celiac children among the 198 who participated in the study (which means a very high prevalence of 3%, higher than the European mean). All of them presented no symptoms at all, or minor imperceptible symptoms which didn’t make their parents consult a pediatrician.

The confirmation of this diagnosis was carried out at the Pediatric Gastroenterology Unit at the Virgen de las Nieves University Hospital (Granada), where those 6 patients underwent endoscopy and biopsy procedures.

“It’s a novel research, given that there are few published works that use these devices in apparently healthy people, in Spain and the rest of Europe –Mª Vega Almazán stresses–. Counting with this kind of diagnostic methods in the family doctor’s or the pediatrician’s office would allow to find cases of celiac disease not diagnosed due to its atypical symptomatology, and to avoid unnecessary procedures, blood extractions or patient referral to specialized doctors”.

Bibliographic references:

Pediatr Res. 2015 Sep;78(3):280-5. doi: 10.1038/pr.2015.98. Epub 2015 May 21.

Link to complete article:

http://www.nature.com/pr/journal/v78/n3/full/pr201598a.html

Contact:

Mª Vega Almazán Fernández de Bobadilla

Departamento de Pediatría de la Universidad de Granada. Centro de Salud de Maracena. (Distrito Granada-Metropolitano)

E-mail: vegalmazanfdb@gmail.com

Researchers from the universities of Granada, Barcelona and Jaen prove that maslinic acid, a natural triterpene found in high concentrations in the waxy skin of olives, is effective, in Caco-2 p53-deficient colon adenocarcinoma cells, in just a few hours

Researchers from the University of Granada (UGR), in collaboration with the universities of Barcelona and Jaen, have brought to light the antitumoral nature of maslinic acid (a compound derived from olives) in Caco-2 p53-deficient colon adenocarcinoma cells in the short term.

Maslinic acid (MA) is a natural triterpene found in high concentrations in the waxy skin of olives, obtained through a method patented by professors Andrés García-Granadados López de Hierro and Andrés Parra Sánchez from the UGR department of Organic Chemistry, and currently used by the company Biomaslinic S.L.

The results of this research, recently published in the renowned PloS ONE magazine, show without a doubt how maslinic acid is capable of early inducing the extrinsic cellular death pathway in Caco-2 cells that don’t express protein p53 (known by its pro-apoptotic capacity).

Said research has been lead by professors José Antonio Lupiáñez Cara and Andrés Parra Sánchez from the University of Granada, Marta Cascante Serratosa from the University of Barcelona, and Juan Peragón Sánchez from the University of Jaen.

In previous works, professor Lupiáñez Cara’s research team had reported that maslinic acid induces apoptotic cell death via the mitochondrial apoptotic pathway in cancer cell lines.

In the paper published in PloS ONE, the researchers have shown that MA induces apoptosis in Caco-2 colon cancer cells via the extrinsic apoptotic pathway in a dose-dependent manner in the short term (4 hours).

A quick response

Maslinic acid triggers a series of effects associated with apoptosis and increased the levels of the pro-apoptotic protein t-Bid within a few hours of its addition to the culture medium. This triterpene has no effect on the expression of the Bax protein or the release of cytochrome-c (proteins involved in the mitochondrial apoptotic pathway), or on the mitochondrial membrane potential.

This suggests that MA triggered the extrinsic apoptotic pathway in this cell type, as opposed to the intrinsic pathway found in the HT29 colon-cancer cell line (cells which do have the tumor suppressor gene p53 and, as a result, express the protein p53.

The results published in PloS ONE suggest that the apoptotic mechanism induced in Caco-2 may be different from that found in HT29 colon-cancer cells, and that in Caco-2 cells maslinic acid seems to work independently of the presence of p53. Natural antitumoral agents capable of activating both the extrinsic and intrinsic apoptotic pathways could be of great use in treating colon-cancer of whatever origin.

The researches currently being carried out by the team are focused on finding compounds chemically derived from maslinic and oleanolic acids which are related with anti proliferative, anti tumoral and anti angiogenic tasks as well as pharmacokinetic tasks at different levels (sub-molecular, molecular and cellular), in order to establish both their mechanism of action and the link between the various by-products and their effect on the cells.

Bibliographic references:

Reyes-Zurita, F.J.; Rufino-Palomares, E.E.; García-Salguero, L.; Peragón, J.; Medina, P.P. Parra, A.; Cascante, M. and Lupiáñez, J.A. (2016): Maslinic acid, a natural triterpene, induces a death receptor-mediated apoptotic mechanism t-Bid depended in Caco-2 p53-deficient colon adenocarcinoma cells.

PLoS ONE 11 (1): e0146178. doi: 10.1371/journal.pone.0146178.

Links to complete article:

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146178

http://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pone.0146178&representation=PDF

Contact:

José Antonio Lupiáñez Cara

Catedrático de Bioquímica y Biología Molecular

Departamento de Bioquímica y Biología Molecular I de la Universidad de Granada.

Telephones: (+34) 958 243 089 – (+34) 958 243 250

E-mail: jlcara@ugr.es

An international team of researchers, with the participation of the University of Granada, reveals new data on why breast cancer has a higher incidence and is more aggressive in obese people

The results were published in the last issue of the renowned Cancer Research magazine

An international team of researchers, with the participation of the University of Granada (UGR), has revealed new data on why breast cancer has a higher incidence and is more aggressive in obese people. The reason is that peritumoral fat (the fat around the tumor) facilitates the expansion and invasion of cancer stem cells (CSCs), which are responsible of the onset and growth of the tumor.

CSCs are found in tumors in a very small proportion, and their main characteristic is that they are responsible of metastasis originating in parts of the body far from the original tumor. Conventional chemotherapy and radiotherapy treatments are not capable of eliminating said CSCs, and for that, it’s very common that, after the first response to the treatment, many cancer patients suffer a relapse.

This new research work has been lead by the University of Miami (Florida, United States), and it has counted with the participation of researchers from Granada’s University Hospital Center and from the UGR “Terapias avanzadas: diferenciación, regeneración y cáncer” (Advanced therapies: differentiation, regeneration and cancer) research team. Both groups of researchers belong to the Biosanitary Institute of Granada (ibs. GRANADA).

Mechanisms yet to be clarified

The consequences of the obesity epidemic on cancer morbidity and mortality are very serious. In fact, it is estimated that, nowadays, up to 20% of cancer-related deaths may be attributable to obesity.

Obese women have a greater risk of suffering breast cancer after menopause, and they have a worse progression of the disease no matter their age, but the mechanisms by which obesity contributes to the development and progression of cancer aren’t clear yet. Obesity-related fat causes local inflammation and prevents adipocytes (the cells forming said fat) from maturing.

For this research, carried out in mice and published in the renowned Cancer Research magazine, researchers assessed the effects of coculturing adipocytes with breast cancer cells on tumor aggressivity, capacity of local invasion and metastatic potential of said tumor.

The results show that the interaction between tumor cells and immature adipocytes near the tumor during the first stages of breast cancer increased the secretion of cytokines (proinflammatory proteins).

“Said cytokines cause a greater expansion of highly metastatic CSCs”, UGR professor Juan Antonio Marchal Corrales, one of the authors of this paper, explains.

Preclinical rationale

In addition, the researchers have described the mechanism by which this process takes place and its relation with the activation of the SRC Kinase protein. In turn, said protein induces the activation of the Sox2 transcription factor (essential to maintain stem cells characteristics) and of a small RNA molecule called miRNA-302b.

“The prolonged coculture of tumor cells with immature adipocytes or cytokines increased the proportion of CSCs (which had the ability to form new tumors), the presence of tumor cells in blood, and the metastatic potential after its implementation in mice –Marchal says–. And last, we found that SRC-Kinase-inhibiting drugs decrease the production of cytokines and CSCs”.

These findings reveal new insights underlying increased breast cancer mortality in obese individuals and provide a novel preclinical rationale to test the efficacy of SRC inhibitors for breast cancer treatment.

Bibliographic references:

Interactions between Adipocytes and Breast Cancer Cells Stimulate Cytokine Production and Drive Src/Sox2/miR-302b–Mediated Malignant Progression

Manuel Picon-Ruiz, Chendong Pan, Katherine Drews-Elger, Kibeom Jang, Alexandra H. Besser, Dekuang Zhao, Cynthia Morata-Tarifa, Minsoon Kim, Tan A. Ince, Diana J. Azzam, Seth A. Wander, Bin Wang, Burcu Ergonul, Ram H. Datar, Richard J. Cote, Guy A. Howard, Dorraya El-Ashry, Pablo Torne-Poyatos, Juan A. Marchal, and Joyce M. Slingerland

Cancer Research 2016 Jan 15; 76(2):491-504.

DOI: 10.1158/0008-5472.CAN-15-0927

Link to complete article (PDF):

http://cancerres.aacrjournals.org/content/early/2016/01/07/0008-5472.CAN-15-0927.long

Contact:

Juan Antonio Marchal Corrales

Departamento de Anatomía y Embriología Humana de la Universidad de Granada

Telephones: (+34) 958 241 000 ext. 20080 – (+34) 958 249 321

Correo electrónico: jmarchal@ugr.es