A Case Series of Pregnant Women With Mitral Stenosis.

Pregnant women with mitral stenosis have a high cardiovascular risk, and their outcomes vary greatly. The management of these patients should be individualized and carried out by a multidisciplinary team. This case series presents 3 cases of pregnant women with severe mitral stenosis, describing their progression and therapeutic strategies.

Protein Translation Inhibition is Involved in the Activity of the Pan-PIM Kinase Inhibitor PIM447 in Combination with Pomalidomide-Dexamethasone in Multiple Myeloma.

Background: Proviral Insertion site for Moloney murine leukemia virus (PIM) kinases are overexpressed in hematologic malignancies, including multiple myeloma. Previous preclinical data from our group demonstrated the anti-myeloma effect of the pan-PIM kinase inhibitor PIM447.

Methods: Based on those data, we evaluate here, by in vitro and in vivo studies, the activity of the triple combination of PIM447 + pomalidomide + dexamethasone (PIM-Pd) in multiple myeloma.

Filanesib for the treatment of multiple myeloma.

: Kinesin spindle protein (KSP) is indispensable for the proper separation of spindle poles during mitosis. Importantly, this protein is expressed only in cells undergoing cell division and hence represents an appealing target for the treatment of cancer. Many KSP inhibitors have demonstrated a strong antitumoral effect , however, they have exhibited only limited activity in clinical trials.

The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma.

Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor of this protein, has demonstrated activity in heavily pre-treated multiple myeloma patients. The aim of the work herein was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect.

Preclinical anti-myeloma activity of EDO-S101, a new bendamustine-derived molecule with added HDACi activity, through potent DNA damage induction and impairment of DNA repair.

Background: Despite recent advances in the treatment of multiple myeloma (MM), the prognosis of most patients remains poor, and resistance to traditional and new drugs frequently occurs. EDO-S101 is a novel therapeutic agent conceived as the fusion of a histone deacetylase inhibitor radical to bendamustine, with the aim of potentiating its alkylating activity.

Methods: The efficacy of EDO-S101 was evaluated in vitro, ex vivo and in vivo, alone, and in combination with standard anti-myeloma agents.

[Physical training in chronic heart failure: pathophysiology and clinical evolution].

Chronic heart failure has become one of the main global health problems; 23 million people suffer from this disease worldwide and age of onset has varied considerably over the past five decades, coinciding with other co-morbidities as longevity in the population increases. Treatment of heart failure has also shown striking variations in recent years. Such is the case of the substitution of sympathomimetic drugs by beta-blocking agents, which primarily means a conceptual change in the pathophysiological interpretation of this syndrome.

Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bortezomib and dexamethasone.

Despite new advances in multiple myeloma treatment and the consequent improvement in overall survival, most patients relapse or become refractory to treatment. This suggests that new molecules and combinations that may further inhibit important survival pathways for these tumor cells are needed. In this context, zalypsis is a novel compound, derived from marine organisms, with a powerful preclinical anti-myeloma effect based on the sensitivity of malignant plasma cells to DNA-damage induction; and it has already been tested in a phase I/II clinical trial in multiple myeloma.

The Novel Pan-PIM Kinase Inhibitor, PIM447, Displays Dual Antimyeloma and Bone-Protective Effects, and Potently Synergizes with Current Standards of Care.

Purpose: PIM kinases are a family of serine/threonine kinases recently proposed as therapeutic targets in oncology. In the present work, we have investigated the effects of the novel pan-PIM kinase inhibitor, PIM447, on myeloma cells and myeloma-associated bone disease using different preclinical models.

Experimental Design: In vitro/ex vivo cytotoxicity of PIM447 was evaluated on myeloma cell lines and patient samples.

Antitumoral effect of Ocoxin on acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy whose incidence is growing in developed countries. In the relapse setting, very limited therapeutic options are available and in most cases only palliative care can be offered to patients. The effect of a composite formulation that contains several antioxidants, Ocoxin Oral solution (OOS), was tested in this condition.

Effect of Oncoxin Oral Solution in HER2-Overexpressing Breast Cancer.

One of the most aggressive breast cancer subtypes includes tumors with high expression of HER2. Gene expression and functional studies have shown a link between HER2 overexpression and oxidative stress. Because of this, we hypothesized that Oncoxin Oral Solution (OOS), a composite product that contains several antioxidants, could have an antitumoral effect against HER2+ tumors.

R-RAS2 overexpression in tumors of the human central nervous system.

Malignant tumors of the central nervous system (CNS) are the 10th most frequent cause of cancer mortality. Despite the strong malignancy of some such tumors, oncogenic mutations are rarely found in classic members of the RAS family of small GTPases. This raises the question as to whether other RAS family members may be affected in CNS tumors, excessively activating RAS pathways.

[Effects of long-term exercise training on left ventricular function and remodeling in patients with anterior wall myocardial infarction].

Objective: To assess the effects of long-term exercise training on the function and remodeling of the left ventricle after myocardial infarction.

Methods: We studied 90 patients with a first acute anterior-wall myocardial infarction, all received conventional medical treatment. Symptom-limited maximal exercise stress tests, echocardiograms and effort-rest isotopic ventriculographies at 2, 6 and 12 months after myocardial infarction were performed; the follow-up time averaged 36.