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Publications (48)
Breast cancer is the most common type of cancer and the leading cause of death among women. Recent evidence suggests that mesenchymal stromal/stem cells and cancer‐associated fibroblasts (CAFs) have an essential role in cancer progression, invasion and therapy resistance. Therefore, they are considered as highly promising future therapeutic targets...
Bone marrow stromal cells provide a proper environment for the development of hematologic lineages. The incorporation of different stromal cells to in vitro culture systems would be an attractive model to study megakaryopoiesis and thrombopoiesis. Our objective was to evaluate the participation of different types of stromal cells on in vitro megaka...
Breast cancer is one of the most common oncological pathologies in women worldwide. While its early diagnosis has considerably improved, about 70% of advanced patients develop bone metastases with a high mortality rate. Several authors demonstrated that primary breast cancer cells prepare their future metastatic niche –known as the pre-metastatic n...
Type 1 diabetes occurs as a consequence of progressive autoimmune destruction of beta cells. A potential treatment for this disease should address the immune attack on beta cells and their preservation/regeneration. The objective of this study was to elucidate whether the immunomodulatory synthetic oligonucleotide IMT504 was able to ameliorate diab...
The immune responses of humans and animals to insults (i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged pro-inflammatory stimuli bringing about chronic inflammation can lead to life-threat...
Type 1 diabetes (T1D) originates from autoimmune β-cell destruction. IMT504 is an immunomodulatory oligonucleotide that increases mesenchymal stem cells cloning capacity and reverts toxic diabetes in rats. Here we evaluated long-term (20 doses) and short-term (2-6 doses) effects of IMT504 (20 mg/kg/day, sc) in an immunodependent diabetes model: mul...
Background:
Despite advances in the study of breast cancer (BC), it remains the second leading cause of mortality among women. BC is a heterogeneous system, mainly composed of tumor epithelial cells (TEpCs) and stromal cells (SCs); the interaction through the ligands and their receptors (Rs) plays a major role in BC progression. The aim of the pre...
Background: Despite recent major advance in the understanding of the mechanisms of breast cancer (BC) progression and in the development of novel therapeutic modalities, BC remains the second leading cause of mortality among women. Mortality is almost invariably due to metastasis. The different histological subtypes of BC and molecular maker expres...
Bone metastasis is the major cause of death for advanced breast cancer patients (BCP). It is a multistep process that includes tumor cell mobilization, intravasation, survival in the circulation, extravasation and proliferation in bone marrow (BM) or bone. Accumulating evidence suggests that BM-mesenchymal stromal cells (MStC) play a critical role...
It has been described that the hematopoietic niche has to be considered as a dynamic system that could easily behave as a tumor niche because they share many structural and functional components. Bone marrow (BM) mesenchymal stem cells (MSC) are one of the actors that regulate homing, migration, proliferation and survival, quiescence and latency of...
Bone metastasis is an incurable complication of breast cancer affecting 70-80 % of advanced patients. It is a multistep process that includes tumour cell mobilisation, intravasation, survival in the circulation, extravasation, migration and proliferation in the bone marrow/bone. Although novel findings demonstrate the bone marrow microenvironment s...
The considerable therapeutic potential of human multipotent mesenchymal stromal cells or mesenchymal stem cells (MSCs) has generated increasing interest in a wide variety of biomedical disciplines. Nevertheless, researchers report studies on MSCs using different methods of isolation and expansion, as well as different approaches to characterize the...
Tumour cells can find in bone marrow (BM) a niche rich in growth factors and cytokines that promote their self-renewal, proliferation and survival. In turn, tumour cells affect the homeostasis of the BM and bone, as well as the balance among haematopoiesis, osteogenesis, osteoclastogenesis and bone-resorption. As a result, growth and survival facto...
Introduction:
Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH...
While breast cancer (BC) is the major cause of death among women worldwide, there is no guarantee of better patient survival because many of these patients develop primarily metastases, despite efforts to detect it in its early stages. Bone metastasis is a common complication that occurs in 65-80 % of patients with disseminated disease, but the mol...
Adipose microenvironment is involved in signaling pathways that influence prostate cancer (PCa) progression. However, the role of human periprostatic adipose tissue (PPAT) from patients with benign prostatic hyperplasia (BPH) has not been studied and compared to that of PPAT from PCa patients. The aim of this paper was to investigate the influence...
We have shown that oligodeoxynucleotide IMT504 improved blood glucose and islet beta-cell content in streptozotocin (STZ)-induced diabetic rats, inducing early expression of progenitor markers. Here we determined the effect of IMT504 on islet infiltration and on immunomodulatory proteins indoleamine 2,3-dioxygenase (IDO) and TNF-α-stimulated gene/p...
Most advanced breast cancer patients (BCP) develop osteolytic bone metastasis as a result of the imbalance between osteogenesis, osteoclastogenesis and bone resorption processes. In bone marrow (BM) aspirates of untreated BCP (infiltrative ductal breast carcinoma, clinical stage III and IV, without bone and BM metastasis), a decrease in cloning eff...
Effect of IMT504 treatment on water (a) and food (b) intakes, BW increase (c) and food efficiency (d) in Control-Saline (black triangles), Control-IMT504 (white squares), STZ-Saline (black squares) and STZ-IMT504 (asterisks) rats. Food and water intakes and BW were recorded at 12:00 hours in non-fasted animals. Food efficiencies were calculated as...
a-c Representative images of insulin staining from each group. d Blood glucose after two consecutive days of blood glucose decrease in STZ-IMT504 (n = 6); Control-Saline (n = 4) and STZ-Saline (n = 6) rats were killed at the same time. One-way ANOVA, p < 0.001; *p < 0.001 significantly different from Control-Saline and STZ-IMT504. Three out of six...
IMT504 is an oligonucleotide that promotes tissue repair in bone injury and neuropathic pain models by stimulating progenitor cells. Here we evaluated the effect of IMT504 on the recovery of islet function in a streptozotocin (STZ)-induced model of diabetes in the rat.
Male Sprague-Dawley rats were injected with STZ (60 mg/kg, i.p., day 1) or citra...
In the last years, significant progress has been made in the medical treatment of pain. However, pathological pains, such us neuropathic pain, remain refractory to the currently available analgesics. Therefore, new therapeutic strategies are being evaluated. We have recently shown that both bone marrow stromal cells (MSCs) and the oligonucleotide I...
Bone marrow mesenchymal stromal cells (BM-MSCs) with regenerative potential have been identified in heart. Whether these cells become new cardiac lineage cells by phenomena of transdifferentiation or fusion is also being investigated. Although, these mechanisms give cardiomyocytes, it has to be considered that MSCs transplantation could carry out o...
We have shown that bone marrow (BM) from untreated advanced lung and breast cancer patients (LCP and BCP) have a reduced number of colony-forming unit fibroblasts (CFU-Fs) or mesenchymal stem cells (MSCs). Factors that regulate the proliferation and differentiation of CFU-F are produced by the patients' BM microenvironment. We have now examined whe...
We have recently shown that the administration of bone marrow stromal cells (MSCs) prevents the development of mechanical and thermal allodynia in animals subjected to a sciatic nerve injury. Furthermore, exogenously administered MSCs have been shown to participate in the repair and regeneration of damaged tissues in a variety of animal models. How...
Bone marrow (BM)-derived adult mesenchymal stem cells (MSCs) have the capacity to differentiate in vitro into different cell lines. This makes them a likely source for application in tissue repair therapies. Here, we report evidence indicating that, both in vivo and in vitro, IMT504, the prototype of the PyNTTTTGT class of immunostimulatory oligonu...
Previously, we reported a deficient cloning capacity of the bone marrow (BM) mesenchymal stem cells to give colony-forming unit fibroblast (CFU-F) and an inefficient confluence capacity of BM stromal cells in advanced untreated lung cancer patients (LCP) and breast cancer patients (BCP). Moreover, a decreased level of bFGF at day 7 in the condition...
Bone marrow (BM) is an important tissue in the generation of immunocompetent and peripheral blood cells. The precursors of hematopoietic cells in BM undergo continuous proliferation and differentiation and are highly vulnerable to acute and chronic oxidative stress. Little is known about the oxidant and antioxidant status in the BM of untreated pat...
We analyzed the ability of the bone marrow (BM) stromal cells to achieve confluence and their proliferative capacity in BM primary cultures from 30 untreated lung cancer patients (LCP), 27 breast cancer patients (BCP), and 30 normal controls (NC) when these confluent cells were induced to proliferate following four continuous subcultures. Moreover,...
In a previous study we demonstrated that the incidence of fibroblast colony-forming units (CFU-F) was very low in bone marrow primary cultures from the majority of untreated advanced non-small lung cancer patients (LCP) compared to normal controls (NC). For this reason, we studied the ability of bone marrow stromal cells to achieve confluence in pr...
BACKGROUND
Although alterations of the bone marrow (BM) fibroblast colony-forming cells are involved in the development of diverse hematologic disorders, these progenitors still have not been well characterized in patients with solid tumors.METHODS
The incidence of fibroblast colony-forming units (CFU-F) was evaluated in the cultures of unseparated...
Although alterations of the bone marrow (BM) fibroblast colony-forming cells are involved in the development of diverse hematologic disorders, these progenitors still have not been well characterized in patients with solid tumors.
The incidence of fibroblast colony-forming units (CFU-F) was evaluated in the cultures of unseparated and fractionated...
Bone marrow fibroblast colony-forming cells (CFU-F) were studied in fifteen consecutive untreated breast cancer patients (BCP) with clinical stages III and IV, and in sixteen normal controls (NC). A decreased number of CFU-F was observed in BCP compared to NC (p < 0.004). Confluence of the adherent cell layer was observed in all normal bone marrow...
We studied the production of interleukin-1 (IL-1) by peripheral blood monocytes (Mo) from twelve normal subjects (NS) and eight and nine untreated lung and colorectal cancer patients (CP), respectively. No significant changes of extracellular IL-1 biological activity was observed between CP and NS by thymocyte proliferation assay. This result was i...
Cultured splenic mononuclear adherent cells (SMAc) from normal BALB/c mice as well as those from mice bearing 10-day sarcoma 180 (S180), exhibited a marked increase in Escherichia coli lipopolysaccharide-stimulated interleukin-1 (IL-1) production, when compared to spontaneous values. On days 20 and 30 following S180 challenge, a decrease in this ef...
Cultured splenic mononuclear adherent cells (SMAc)from normal BALB/c mice as well as those from mice bearing 10-day sarcoma 180 (S180), exhibited a marked increase in Escherichia coli lipopolysaccharide-stimulated interleukin-1 (IL-1) production, when compared to spontaneous values. On days 20 and 30 following S180 challenge, a decrease in this eff...
We studied the production of chemiluminescence (CL) by peripheral blood neutrophils from 24 normal subjects, 13 lung cancer patients with clinical stages (CS) III and IV, and 27 breast cancer patients with CS II, III, and IV. Evaluations were made before chemo- and radiotherapy treatments. CL was expressed as: baseline of the record background acti...
The production of IL-1 by splenic mononuclear adherent cells (MAC) from BALB/c mice inoculated with Sarcoma 180 (S180) was examined as a possible mechanism underlying the immunosuppression observed in tumor bearing mice. Two different inducers of IL-1 were used to stimulate MAC. A natural polysaccharide PCj3 (1, 5, 10 micrograms/ml) and a lipopolys...
The antitumoral activity of the polysaccharide (PCj3) isolated from the Cyttaria johowii fungus on the growth of solid Sarcoma 180 (S180) in normal and splenectomized BALB/c mice was studied, observing that this treatment inhibited tumor growth in normal and splenectomized mice. At the same time, the effect of PCj3 on peripheral blood leukocyte pop...
The effect of a polysaccharide (PCj3), isolated from the ascomycete "Cyttaria johowii" was studied on the growth of the ascitic Sarcoma 180 (S180) inoculated subcutaneously in BALB/c mice which had been previously splenectomized. The leukocyte alterations in peripheral blood were analyzed simultaneously, and the percentage of cells with C3b recepto...
Serum circulating immune complexes (CIC) were measured in 27 patients with non insulin dependent diabetes (NIDD). This was done by measuring the degree of binding to human red blood cells by the C3b complement fraction. At the same time, the percentage of B lymphocytes in peripheral blood was evaluated by means of the direct immunofluorescence tech...
