Cardiac wasting in head and neck cancer and in cardiac autopsies from different cancer types: A study in a chemo-naïve setting.

Background: Cardiac wasting is a detrimental consequence of cancer that has been traditionally ignored and often misinterpreted as an iatrogenic effect.

Methods: We conducted a retrospective study on 42 chemo-naive patients affected by locally advanced head and neck cancer (HNC). Based on unintentional weight loss, patients were divided into cachectic and non-cachectic.

Development of Cancer in Patients With Heart Failure: How Systemic Inflammation Can Lay the Groundwork.

In the last decade, cardiologists and oncologists have provided clinical and experimental evidence that cancer, and not only chemotherapeutic agents, can cause detrimental effects on heart structure and function, a consequence that has serious clinical implications for patient management. In parallel, the intriguing idea that heart failure (HF) may be an oncogenic condition has also received growing attention. A number of epidemiological and clinical studies have reported that patients with HF have a higher risk of developing cancer.

How progressive cancer endangers the heart: an intriguing and underestimated problem.

Since it came into being as a discipline, cardio-oncology has focused on the prevention and treatment of cardiotoxicity induced by antitumor chemotherapy and radiotherapy. Over time, it has been proved that even more detrimental is the direct effect generated by cancer cells that release pro-cachectic factors in the bloodstream. Secreted molecules target different organs at a distance, including the heart.

Myocardial overexpression of ANKRD1 causes sinus venosus defects and progressive diastolic dysfunction.

Aims: Increased Ankyrin Repeat Domain 1 (ANKRD1) levels linked to gain of function mutations have been associated to total anomalous pulmonary venous return and adult cardiomyopathy occurrence in humans. The link between increased ANKRD1 level and cardiac structural and functional disease is not understood. To get insight into this problem, we have generated a gain of function ANKRD1 mouse model by overexpressing ANKRD1 in the myocardium.

Turning science into teaching: a challenge for scientists.

This article was migrated. The article was marked as recommended. Teaching basic science in the medical school remains a challenge, and the lack of appropriate resources is one of important limitation.

Multicenter research into the quality of life of patients with advanced oropharyngeal carcinoma with long-term survival associated with human papilloma virus.

The treatment of advanced-stage oropharyngeal squamous cell carcinoma may utilize various modes, including combining surgery with chemoradiotherapy (CTRT), or primary CTRT followed by rescue surgery. In previous literature it has been revealed how patients treated with combined modes report a low quality of life (QoL) and severe consequences following surgery, radiotherapy and chemotherapy, in the short and in the long-term. The decrease in the QoL of patients treated with high-intensity multi-modal strategies highlights the necessity of modifying treatments, particularly for young HPV-positive patients, where an increased survival rate has already been reported.

Optimized protocol for immunostaining of experimental GFP-expressing and human hearts.

Morphological and histochemical analysis of the heart is fundamental for the understanding of cardiac physiology and pathology. The accurate detection of different myocardial cell populations, as well as the high-resolution imaging of protein expression and distribution, within the diverse intracellular compartments, is essential for basic research on disease mechanisms and for the translatability of the results to human pathophysiology. While enormous progress has been made on the imaging hardware and methods and on biotechnological tools [e.

Targeting cellular and molecular drivers of head and neck squamous cell carcinoma: current options and emerging perspectives.

Despite improvements in functional outcomes attributable to advances in radiotherapy, chemotherapy, surgical techniques, and imaging techniques, survival in head and neck squamous cell carcinoma (HNSCC) patients has improved only marginally during the last couple of decades, and optimal therapy has yet to be devised. Genomic complexity and intratumoral genetic heterogeneity may contribute to treatment resistance and the propensity for locoregional recurrence. Countering this, it demands a significant effort from both basic and clinical scientists in the search for more effective targeted therapies.

The cardiovascular unit as a dynamic player in disease and regeneration.

Cell-mediated cardiac regeneration remains a challenge as a therapeutic option in heart failure, but modest success using experimental models suggests that a better understanding of normal histogenesis will be needed to make progress towards cardiac regeneration. Recent studies of the heart show that the interstitium informs organogenesis and responsiveness to pathological stimuli through continuous bidirectional cross-talk between cardiomyocytes and non-cardiac cells. Here, we introduce the concept of the "cardiovascular unit" (CVU) as a building block of the heart, which includes cardiomyocytes and adjacent capillaries and fibroblasts.

From fish to amphibians to mammals: in search of novel strategies to optimize cardiac regeneration.

Different vertebrate species have different cardiac regeneration rates: high in teleost fish, moderate in urodele amphibians, and almost negligible in mammals. Regeneration may occur through stem and progenitor cell differentiation or via dedifferentiation with residual cardiomyocytes reentering the cell cycle. In this review, we will examine the ability of zebrafish and newts to respond to cardiac damage with de novo cardiogenesis, whereas rodents and humans respond with a marked fibrogenic response and virtually no cardiomyocyte regeneration.

Cardiac interstitial cells express GATA4 and control dedifferentiation and cell cycle re-entry of adult cardiomyocytes.

Interstitial cells of the adult rat heart were characterized with respect to i) expression of cardiac markers of commitment and differentiation, ii) myogenic potential in vitro and iii) ability to modulate cardiomyocyte differentiation state. We demonstrate for the first time that fibroblasts and a proportion of pericytes in the adult rat heart express the transcription factor GATA4. This appears to be a peculiar property of the heart.

In vivo delivery of naked antisense oligos in aged mdx mice: analysis of dystrophin restoration in skeletal and cardiac muscle.

Antisense-mediated exon skipping holds great potential for the treatment of DMD. In mdx mice, functional recovery of skeletal muscle has been obtained upon systemic delivery of "naked" oligonucleotides or viral vectors encoding for antisense snRNAs. However, amongst the studies reported so far, which used either neonatal or young adult animals--only one achieved dystrophin restoration in cardiac muscle, using an adeno-associated vector.

A lentiviral vector with a short troponin-I promoter for tracking cardiomyocyte differentiation of human embryonic stem cells.

Human embryonic stem cells (hESCs) may become important for cardiac repair due to their potentially unlimited ability to generate cardiomyocytes (CMCs). Moreover, genetic manipulation of hESC-derived CMCs would be a very promising technique for curing myocardial disorders. At the present time, however, inducing the differentiation of hESCs into CMCs is extremely difficult and, therefore, an easy and standardizable technique is needed to evaluate differentiation strategies.

GATA elements control repression of cardiac troponin I promoter activity in skeletal muscle cells.

Background: We reported previously that the cardiac troponin I (cTnI) promoter drives cardiac-specific expression of reporter genes in cardiac muscle cells and in transgenic mice, and that disruption of GATA elements inactivates the cTnI promoter in cultured cardiomyocytes. We have now examined the role of cTnI promoter GATA elements in skeletal muscle cells.

Results: Mutation or deletion of GATA elements induces a strong transcriptional activation of the cTnI promoter in regenerating skeletal muscle and in cultured skeletal muscle cells.

Age is a risk factor for maladaptive changes in rats exposed to increased pressure loading of the right ventricular myocardium.

Objective: To study the adaptive potential of the right ventricular myocardium after 30 days of mechanical-induced overload in rats from two different age groups.

Materials And Methods: We banded the pulmonary trunk, so as to increase the systolic work load of the right ventricle, in 19 adult Sprague-Dawley rats at the age of 10 weeks, and 16 weanlings when they were 3 weeks-old, using 10 adults and 10 weanlings as controls. We analysed the functional adaptation and structural changes of the right ventricular myocardium, blood vessels and interstitial tissue after 30 days of increased afterload.

Hybrid cardiomyocytes derived by cell fusion in heterotopic cardiac xenografts.

Cardiomyocytes expressing host markers, such as the Y chromosome in sex-mismatched transplants, have been described in human allografts, suggesting that circulating cells can contribute to cardiac regeneration. It has not been established, however, whether host-derived cardiomyocytes result from transdifferentiation of stem cells or cell fusion. To address this issue, we used heterotopic heart xenografts and looked for markers of donor and recipient cells.

Differential availability/processing of decorin precursor in arterial and venous smooth muscle cells.

The existence of specific differentiation markers for arterial smooth muscle (SM) cells is still a matter of debate. A clone named MM1 was isolated from a library of monoclonal antibodies to adult porcine aorta, which in vivo binds to arterial but not venous SM cells, except for the pulmonary vein. MM1 immunoreactivity in Western blotting involved bands in the range of M(r) 33-226 kDa, in both arterial and venous SM tissues.

Host-derived circulating cells do not significantly contribute to cardiac regeneration in heterotopic rat heart transplants.

Objectives: The aim of this study was to investigate the contribution of host-derived circulating cells to cardiac repair after tissue damage using the model of heterotopic heart transplantation between transgenic recipient rats expressing green fluorescent protein (GFP) and wild-type donors.

Methods: Unlabeled donor rat hearts, some of which underwent prolonged cold ischemia pretreatment, were transplanted into the abdominal cavity of GFP+ transgenic recipient rats and were analyzed 15 and 90 days after surgery. An additional experimental group underwent heart transplantation following administration of granulocyte-colony stimulatory factor (G-CSF) to mobilize bone marrow cells.

A new nested primer pair improves the specificity of CK-19 mRNA detection by RT-PCR in occult breast cancer cells.

Reverse transcription polymerase chain reaction (RT-PCR) of cytokeratin-19 (CK-19) has been widely used to detect small numbers of circulating malignant epithelial cells in the bone marrow or the peripheral blood of patients with breast cancer. However, a high percentage of false positive results has been recorded and conflicting reports question the clinical relevance of this technical approach. We demonstrate that the use of a new nested primer pair for CK-19 RT-PCR avoids false positive results without affecting the sensitivity of the assay.

The impact of progenitor enrichment, serum, and cytokines on the ex vivo expansion of mobilized peripheral blood stem cells: a controlled trial.

The aim of this study was to verify, and possibly improve, culture conditions to expand human mobilized peripheral blood stem cells (PBSCs). We investigated the role of three parameters: A) the culture medium (serum-free versus serum-dependent); B) the initial cell population (Ficoll-separated mononucleated cells versus CD34(+)-selected cells), and C) the low concentration of recombinant cytokines, flt3 ligand, and thrombopoietin in association with a basic cocktail of stem cell factor, interleukin (IL)-6, IL-3, GM-CSF, and erythropoietin. Eighteen leukapheresis samples were monitored in static culture for 15 days.

Contribution of adventitial fibroblasts to neointima formation and vascular remodeling: from innocent bystander to active participant.

The adventitial layer surrounding the blood vessels has long been exclusively considered a supporting tissue the main function of which is to provide adequate nourishment to the muscle layers of tunica media. Although functionally interconnected, the adventitial and medial layers are structurally interfaced at the external elastic lamina level, clearly distinguishable at the maturational phase of vascular morphogenesis. Over the last few years the "passive" role that the adventitia seemed to play in experimental and spontaneous vascular pathologies involving proliferation, migration, differentiation, and apoptosis of vascular smooth muscle cells (VSMCs) has been questioned.

Cell lineages and tissue boundaries in cardiac arterial and venous poles: developmental patterns, animal models, and implications for congenital vascular diseases.

Multiple cell populations with different embryological histories are involved in the morphogenesis of the cardiac arterial and venous poles as well as in the correct alignment and connection of the developing vessels with the cardiac chambers. Formation of the aorta and the pulmonary trunk is a complicated process orchestrated via a specific sequence of highly integrated spatiotemporal events of cell proliferation, migration, differentiation, and apoptosis. The peculiar susceptibility of this intricate cell network to be altered explains the frequency of congenital cardiovascular diseases of the arterial and venous poles.

An atrioventricular canal domain defined by cardiac troponin I transgene expression in the embryonic myocardium.

During early cardiac development the atrial myocardium is continuous with the ventricular myocardium throughout the atrioventricular canal. The atrioventricular canal undergoes complex remodelling involving septation, formation of atrioventricular valves and insulation between atria and ventricles except at the level of the atrioventricular node. Understanding of these processes has been hampered by the lack of markers specific for this heart region.

Cardiac and smooth muscle cell contribution to the formation of the murine pulmonary veins.

Previous studies have demonstrated that the primordial pulmonary veins originate as an outgrowth of the atrial cells and anastomosis with the pulmonary venous plexus. As a consequence of this embryologic origin the tunica media of these vessels is composed of cardiac cells that express atrial specific markers (Lyons et al. [1990] J Cell Biol 111:2427-2436; Jones et al.