All-trans retinoic acid and protein kinase C α/β1 inhibitor combined treatment targets cancer stem cells and impairs breast tumor progression.

Breast cancer is the leading cause of cancer death among women worldwide. Blocking a single signaling pathway is often an ineffective therapy, especially in the case of aggressive or drug-resistant tumors. Since we have previously described the mechanism involved in the crosstalk between Retinoic Acid system and protein kinase C (PKC) pathway, the rationale of our study was to evaluate the effect of combining all-trans-retinoic acid (ATRA) with a classical PCK inhibitor (Gö6976) in preclinical settings.

The Bipartite Medial Cuneiform.

This report discusses an unusual case of a 23-year-old woman with a painful bipartite medial cuneiform and severe arthritic and cystic changes at the partition with no history of trauma. Magnetic resonance imaging confirmed a large cyst with subchondral erosions at the dorsal and plantar segments with significant bone marrow edema. Definitive treatment consisted of arthrodesis on the dorsal to plantar segments using one lag screw, demineralized bone matrix grafting, and a bone stimulator.

Antibiotic-loaded bone cement is associated with a lower risk of revision following primary cemented total knee arthroplasty: an analysis of 731,214 cases using National Joint Registry data.

Aims: Antibiotic-loaded bone cements (ALBCs) may offer early protection against the formation of bacterial biofilm after joint arthroplasty. Use in hip arthroplasty is widely accepted, but there is a lack of evidence in total knee arthroplasty (TKA). The objective of this study was to evaluate the use of ALBC in a large population of TKA patients.

Use of Anticoagulants Remains a Significant Threat to Timely Hip Fracture Surgery.

Introduction: Hip fracture remains the biggest single source of morbidity and mortality in the elderly trauma population, and any intervention focused on quality improvement and system efficiency is beneficial for both patients and clinicians. Two of the variables contributory to improving care and efficiency are time to theater and length of stay, with the overall goal being to improve care as reflected within the achievement of best practice tariff. One of the biggest barriers to optimizing these variables is preinjury anticoagulation.

Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology.

Lung cancer (LC) remains the leading cause of cancer mortality worldwide, and non-small cell LC (NSCLC) represents 80% of all LC. Oxidative stress and inflammation, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen activated protein kinases (MAPK) participate in LC pathophysiology. Currently available treatment for LC is limited and in vivo models are lacking.

"Early Trigger" Intravenous Vitamin K: Optimizing Target-Driven Care in Warfarinised Patients With Hip Fracture.

Best practice tariff (BPT) was introduced as a financial incentive model to improve compliance with evidence-based care, such as operation for hip fracture within 36 hours of admission. We previously evaluated the impact of warfarin on patients with hip fracture, revealing significant delay to operation and subsequent loss of revenue. As a result of this, an "early trigger" intravenous vitamin K (IVK) pathway was introduced and the service reaudited a year later.

Differential response of myeloid-derived suppressor cells to the nonsteroidal anti-inflammatory agent indomethacin in tumor-associated and tumor-free microenvironments.

Myeloid-derived suppressor cells (MDSCs) are key regulatory cells that control inflammation and promote tumor-immune escape. To date, no specific immunomodulatory drug has proven efficacy in targeting the expansion and/or function of these cells in different pathophysiologic settings. In this study, we identified a context-dependent effect of the nonsteroidal anti-inflammatory drug indomethacin (IND) on MDSCs, depending on whether they were derived from tumor microenvironments (TME) or from tumor-free microenvironments (TFME).

Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness.

Cachexia is a relevant comorbid condition of chronic diseases including cancer. Inflammation, oxidative stress, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPK) are involved in the pathophysiology of cancer cachexia. Currently available treatment is limited and data demonstrating effectiveness in in vivo models are lacking.

Modulation of pancreatic tumor potential by overexpression of protein kinase C β1.

Objective: This study aimed to investigate whether the overexpression of protein kinase C β1 (PKCβ1) is able to modulate the malignant phenotype displayed by the human ductal pancreatic carcinoma cell line PANC1.

Methods: PKCβ1 overexpression was achieved using a stable transfection approach. PANC1-PKCβ1 and control cells were analyzed both in vitro and in vivo.

Recent changes of the Earth's core derived from satellite observations of magnetic and gravity fields.

To understand the dynamics of the Earth's fluid, iron-rich outer core, only indirect observations are available. The Earth's magnetic field, originating mainly within the core, and its temporal variations can be used to infer the fluid motion at the top of the core, on a decadal and subdecadal time-scale. Gravity variations resulting from changes in the mass distribution within the Earth may also occur on the same time-scales.

Prospective evaluation of a clinical practice guideline for diagnosis of appendicitis in children.

Objectives: The objective was to assess the performance of a clinical practice guideline for evaluation of possible appendicitis in children. The guideline incorporated risk stratification, staged imaging, and early surgical involvement in high-risk cases.

Methods: The authors prospectively evaluated the clinical guideline in one pediatric emergency department (ED) in a general teaching hospital.

Anti-tumor effect of SLPI on mammary but not colon tumor growth.

Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that was related to cancer development and metastasis dissemination on several types of tumors. However, it is not known the effect of SLPI on mammary and colon tumors. The aim of this study was to examine the effect of SLPI on mammary and colon tumor growth.

Hereditary multiple exostoses with spine involvement in a 4-year-old boy.

Hereditary multiple exostosis (HME) is an autosomal dominant disorder characterized by multiple osteochondromas. We describe a case of acute cervical spinal cord compression arising from an exostosis at the lamina of C7 and T1 in a 4-year-old Mexican-American boy with HME. His affected sibling also displayed spinal cord compression because of a bony exostosis.

A follow-up study of MPS I patients treated with laronidase enzyme replacement therapy for 6 years.

Recombinant human alpha-L-iduronidase (Aldurazyme, laronidase) was approved as an enzyme replacement therapy for patients with the lysosomal storage disorder, mucopolysaccharidosis I (MPS I). In order to assess the long-term safety and efficacy of laronidase therapy, 5 of 10 patients in the original laronidase Phase 1/2 clinical trial were re-evaluated after 6 years of treatment. Lysosomal storage was further improved at 6 years (urinary glycosaminoglycans (GAG) excretion decreased 76%; mean liver size at 1.

Inhibition of tumor progression and paraneoplastic syndrome development in a murine lung adenocarcinoma by medroxyprogesterone acetate and indomethacin.

Mice bearing LP07 lung adenocarcinoma present some characteristics similar to those shown in patients with several malignant diseases. LP07 tumor bearers develop paraneoplastic syndromes such as cachexia, leukocytosis, and hypercalcemia, partly due to a systemic inflammatory response. We analyzed some of the mechanisms involved in the effectiveness of the association of the appetite-stimulant medroxiprogesterone acetate (MPA) and the nonselective cyclooxigenase (COX) inhibitor indomethacin (INDO) in LP07 tumor bearing mice.

Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs.

Mice bearing LP07 lung adenocarcinoma show some characteristics that are similar to those present in patients with NSCLC. LP07 tumor-bearing mice develop the paraneoplastic syndromes of cachexia, leukocytosis and hypercalcemia. These symptoms may be partly due to a systemic inflammatory response.

Malignant myoepithelial cells are associated with the differentiated papillary structure and metastatic ability of a syngeneic murine mammary adenocarcinoma model.

Background: The normal duct and lobular system of the mammary gland is lined with luminal and myoepithelial cell types. Although evidence suggests that myoepithelial cells might suppress tumor growth, invasion and angiogenesis, their role remains a major enigma in breast cancer biology and few models are currently available for exploring their influence. Several years ago a spontaneous transplantable mammary adenocarcinoma (M38) arose in our BALB/c colony; it contains a malignant myoepithelial cell component and is able to metastasize to draining lymph nodes and lung.

Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study.

Systemic syndromes characterized by a persistent activity of circulating mediators (cytokines) are frequently present with advanced cancer. We grouped under the general heading of "Systemic Immune-Metabolic Syndrome (SIMS)" a particular variety of distressing systemic syndrome characterized by dysregulation of the psycho-neuro-immune-endocrine homeostasis, with overlapping clinical manifestations. SIMS may include cachexia, anorexia, nausea, early satiety, fatigue, tumor fever, cognitive changes and superinfection.

GM-CSF secreted by murine adenocarcinoma cells modulates tumor progression and immune activity.

During tumor development, growth factors may act in autocrine manner stimulating cell proliferation, or in paracrine manner affecting the microenvironment of the tumor and modulating the immune system. Murine mammary adenocarcinoma M3 tumor bearers develop lung metastases and leukocytosis during its evolution. Previously we described that M3 conditioned media enhanced metastasis incidence, when it was inoculated in tumor-operated mice.

Intramedullary abscess of the spinal cord in children: a case report and review of the literature.

A case report of an intramedullary spinal cord abscess in a 13-month-old boy and a review of relevant existing pediatric literature is presented. Thirty-eight cases of pediatric intramedullary spinal cord abscess are analyzed for presenting signs and symptoms, microbiology of isolated organisms, surgical intervention, antibiotic administration and outcome. The most significant variable on outcome is timely surgical intervention, followed by appropriate antibiotic administration.

Arginine metabolic pathways involved in the modulation of tumor-induced angiogenesis by macrophages.

Neovascularization, an essential step for tumor progression and metastasis development, can be modulated by the presence of macrophages (Mps) in the tumor microenvironment. The ability of Mps to regulate the angiogenicity of the LMM3 tumor cell line was studied. Peritoneal Mps from LMM3 tumor-bearing mice (TMps) potentiate in vivo LMM3 angiogenicity.

Immune reactivity during the growth of a murine lung adenocarcinoma: evaluation of paraneoplastic syndrome development.

The purpose of this study was to investigate if specific immune responses were present in mice bearing a lung adenocarcinoma that presents paraneoplastic syndromes during tumor evolution. Leukocytosis, mainly due to polymorphonuclear leukocytes, was found from day 15 of tumor growth. Delayed type hypersensitivity response and increased interleukin-6 (IL-6) serum levels were observed along tumor growth.

Expression of CD44 splice variants in spontaneous murine tumors.

CD44 is a widely distributed set of cell surface glycoproteins expressed in several types of cells and tissues, implicated in cell-cell and cell-substrate interactions. This molecule plays a major role in cell differentiation, development and activation and has also been described as a potential marker of malignancy and metastasis. In the present study we investigated by RT-PCR followed by exon specific amplification the expression of CD44 splice variants in four different murine tumors as well as in the invaded organs in order to correlate the expression of CD44 variants with potential tumor invasiveness and their implications for growth.

New murine cell line derived from a spontaneous lung tumor induces paraneoplastic syndromes.

LP07 is a new cell line derived from P07 lung tumor, spontaneously arisen in a BALB/c mouse. LP07 is composed of heterogeneous epithelioid polyhedric cells that proliferate at a slow rate, have low plating efficiency and are unable to grow in soft agar. Only some LP07 cells expressed cytokeratins while most of them were positive for vimentin.