Complications of limb salvage surgery in childhood tumors and recommended solutions

Bone and soft tissue malignancies are associated with serious diagnostic and therapeutic problems in every level of pubertal growth in children. Current treatment modality preferred in bone and soft tissue tumors is wide resection of tumor followed by the reconstruction of consequent defect by various methods. Chemotherapy and radiotherapy are applied for systemic effects to the patient pre- and post-operatively and for local effects that facilitate the surgical procedure. Mostly, it is very difficult to control problems following wide resection and reconstruction. In this study, our aim is to discuss the problems encountered in different resection and reconstruction approaches in childhood bone and soft tissue tumors, and the recommended solutions addressed to these problems. From 1990 to 2003, a total of 68 patients (38 female, 30 male) with a mean age of 13.1 (1.5–18) were included in the study. 85.3% of patients were diagnosed as osteosarcoma and the rest was Ewing’s sarcoma. Seventy-five percent of patients had stage IIB disease. The lesions of 34 patients were detected to be in distal femur, 26 in proximal tibia and fibula, 4 in foot and ankle joint, and the remaining 4 in pelvis. As reconstructive surgery, 40 patients had modular prosthesis, vascularized fibular graft was performed in 13 patients, and 10 patients underwent arthrodesis with vascularized fibular graft. 20.6% of patients had shortened limb, infection was detected in 4 patients, laxity in 5, and restricted motion in 4 as complication of prosthesis. With sacrificed physis, 13 patients had a mean value of 4.6 cm limb shortness. Limb salvage surgery has been considered as the gold standard treatment in orthopedic oncological surgery. More understanding of the biology of sarcoma, introduction of new effective chemotherapeutic agents, development of new techniques concerning the surgical resection, advances in diagnostic methods, and improvements in reconstructive surgery all make a major contribution to limb salvage surgery. Since some problems are still encountered, we offer a therapeutic algorithm for complications in the management of childhood tumors that we have encountered so far

Complete Experimental Structure Determination of the p(3x2)pg Phase of Glycine on Cu{110}

We present a quantitative low energy electron diffraction (LEED) surface-crystallograpic study of the complete adsorption geometry of glycine adsorbed on Cu{110} in the ordered p(3×2) phase. The glycine molecules form bonds to the surface through the N atoms of the amino group and the two O atoms of the de-protonated carboxylate group, each with separate Cu atoms such that every Cu atom in the first layer is involved in a bond. Laterally, N atoms are nearest to the atop site (displacement 0.41 Å). The O atoms are asymmetrically displaced from the atop site by 0.54 Å and 1.18 Å with two very different O-Cu bond lengths of 1.93 Å and 2.18 Å. The atom positions of the upper-most Cu layers show small relaxations within 0.07 Å of the bulk-truncated surface geometry. The unit cell of the adsorbate layer consists of two glycine molecules, which are related by a glide-line symmetry operation. This study clearly shows that a significant coverage of adsorbate structures without this glide-line symmetry must be rejected, both on the grounds of the energy dependence of the spot intensities (LEED-IV curves) and of systematic absences in the LEED pattern

Dexmedetomidine as a Sedative in the Awake Implantation of a Neuromodulative System

Objective: During implantation of a neuromodulative system, high patient satisfaction is closely associated with the equilibrium between an effective analgesia and sedation regimen, and the possibility for the patient to be awake and cooperative during procedure. This study assessed the efficacy of the sedative dexmedetomidine to achieve this balance, with patient satisfaction as the primary outcome. Methods: Ten patients undergoing implantation of a dorsal column and dorsal root ganglion stimulator received dexmedetomidine (1 mcg/kg over 10 minutes, followed by 0.6 mcg/kg/hour) in combination with remifentanil at a set dose (3 mcg/kg/hour). Sedation was titrated to a Ramsay Sedation Score of 3. Recorded were as follows: patient satisfaction score, patient comfort score, operator comfort score, pain score, rescue medication and number of adjustments of dexmedetomidine intra-operatively, as well as sedation level, hemodynamic (blood pressure and heart rate), and respiratory characteristics (SpO2). Results: Scores were high on patient satisfaction (me

The partial oxidation of methane over Pd/Al2O3 catalyst nanoparticles studied in-situ by near ambient-pressure x-ray photoelectron spectroscopy

Near ambient-pressure X-ray photoelectron spectroscopy (NAP-XPS) is used to study the chemical state of methane oxidation catalysts in-situ. Al2O3{supported Pd catalysts are prepared with different particle sizes ranging from 4 nm to 10 nm. These catalysts were exposed to conditions similar to those used in the partial oxidation of methane (POM) to syn-gas and simultaneously monitored by NAP-XPS and mass spectrometry. NAP-XPS data show changes in the oxidation state of the palladium as the temperature in- creases, from metallic Pd0 to PdO, and back to Pd0. Mass spectrometry shows an increase in CO production whilst the Pd is in the oxide phase, and the metal is reduced back under presence of newly formed H2. A particle size effect is observed, such that CH4 conversion starts at lower temperatures with larger sized particles from 6 nm to 10 nm. We find that all nanoparticles begin CH4 conversion at lower temperatures than polycrystalline Pd foil

Molecular alterations in key-regulator genes among patients with T4 breast carcinoma

Background: Prognostic factors in patients who are diagnosed with T4 breast carcinomas are widely awaited. We here evaluated the clinical role of some molecular alterations involved in tumorigenesis in a well-characterized cohort of T4 breast cancer patients with a long follow-up period. Methods: A consecutive series of 53 patients with T4 breast carcinoma was enrolled between 1992 and 2001 in Sardinia, and observed up for a median of 125 months. Archival paraffin-embedded tissue sections were used for immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analyses, in order to assess alterations in expression levels of survivin, p53, and pERK1-2 proteins as well as in amplification of CyclinD1 and h-prune genes. The Kaplan-Meier and Cox regression methods were used for survival assessment and statistical analysis. Results: Overall, patients carrying increased expression of pERK1-2 (p = 0.027) and survivin (p = 0.008) proteins as well as amplification of h-prune gene (p = 0.045) presented a statistically-significant poorer overall survival in comparison with cases found negative for such alterations. After multivariate analysis, the pathological response to primary chemotherapy and the survivin overexpression in primary carcinoma represented the main parameters with a role as independent prognostic factors in our series. Conclusions: Although retrospective, our study identified some molecular parameters with a significant impact on prediction of the response to therapy or prognosis among T4 breast cancer patients. Further large prospective studies are needed in order to validate the use of such markers for the management of these patients

Potential prognostic value of heat-shock protein 90 in the presence of phosphatidylinositol-3-kinase overexpression or loss of PTEN, in invasive breast cancers

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Introduction Evaluating the expression of signaling molecule proteins from the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol-3-kinase (PI3K) pathway in invasive breast cancers may identify prognostic marker(s) associated with early relapse. Methods Immunohistochemical analyses of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), PI3K-p110α, phospho-AKT, phospho-p70S6 kinase, phospho-S6 ribosomal protein, phospho-RAF, phospho-p44/42 MAPK, and heat-shock protein 90 (HSP90) were performed on tumor samples from 212 patients with invasive breast cancer. Statistically significant relations between protein expression, clinicopathologic factors, and relapse-free survival (RFS) were analyzed. Results Expression of HSP90 was associated with 5-year RFS, as well as T stage, N stage, histologic grade, estrogen receptor (ER) expression, human epidermal growth factor receptor 2 (HER2) expression, and the Ki-67 proliferation index. On multivariate analysis, coexpression of HSP90 and PI3K-p110α or expression of HSP90 along with PTEN loss demonstrated significantly worse RFS. In subgroup analyses, both exhibited strong prognostic significance in HER2-positive cases, but not in HER2-negative cases. Conclusions The coexpression of HSP90 with PI3K-p110α or expression of HSP90 along with PTEN loss has a potential as a molecular prognostic marker to predict early relapse in patients with invasive breast cancers

High efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor model

Copyright: Copyright 2014 Elsevier B.V., All rights reserved.Background: The combination of virotherapy and chemotherapy may enable efficient tumor regression that would be unachievable using either therapy alone. In this study, we investigated the efficiency of transgene delivery and the cytotoxic effects of alphaviral vector in combination with 5-fluorouracil (5-FU) in a mouse mammary tumor model (4 T1).Methods: Replication-deficient Semliki Forest virus (SFV) vectors carrying genes encoding fluorescent proteins were used to infect 4 T1 cell cultures treated with different doses of 5-FU. The efficiency of infection was monitored via fluorescence microscopy and quantified by fluorometry. The cytotoxicity of the combined treatment with 5-FU and alphaviral vector was measured using an MTT-based cell viability assay. In vivo experiments were performed in a subcutaneous 4 T1 mouse mammary tumor model with different 5-FU doses and an SFV vector encoding firefly luciferase.Results: Infection of 4 T1 cells with SFV prior to 5-FU treatment did not produce a synergistic anti-proliferative effect. An alternative treatment strategy, in which 5-FU was used prior to virus infection, strongly inhibited SFV expression. Nevertheless, in vivo experiments showed a significant enhancement in SFV-driven transgene (luciferase) expression upon intratumoral and intraperitoneal vector administration in 4 T1 tumor-bearing mice pretreated with 5-FU: here, we observed a positive correlation between 5-FU dose and the level of luciferase expression.Conclusions: Although 5-FU inhibited SFV-mediated transgene expression in 4 T1 cells in vitro, application of the drug in a mouse model revealed a significant enhancement of intratumoral transgene synthesis compared with 5-FU untreated mice. These results may have implications for efficient transgene delivery and the development of potent cancer treatment strategies using alphaviral vectors and 5-FU.publishersversionPeer reviewe

Doxorubicin and paclitaxel enhance the antitumor efficacy of vaccines directed against HER 2/neu in a murine mammary carcinoma model

INTRODUCTION: The purpose of the present study was to determine whether cytotoxic chemotherapeutic agents administered prior to immunotherapy with gene vaccines could augment the efficacy of the vaccines. METHODS: Mice were injected in the mammary fat pad with an aggressive breast tumor cell line that expresses HER2/neu. The mice were treated 3 days later with a noncurative dose of either doxorubicin or paclitaxel, and the following day with a gene vaccine to HER2/neu. Two more doses of vaccine were given 14 days apart. Two types of gene vaccines were tested: a plasmid vaccine encoding a self-replicating RNA (replicon) of Sindbis virus (SINCP), in which the viral structural proteins were replaced by the gene for neu; and a viral replicon particle derived from an attenuated strain of Venezuelan equine encephalitis virus, containing a replicon RNA in which the Venezuelan equine encephalitis virus structural proteins were replaced by the gene for neu. RESULTS: Neither vaccination alone nor chemotherapy alone significantly reduced the growth of the mammary carcinoma. In contrast, chemotherapy followed by vaccination reduced tumor growth by a small, but significant amount. Antigen-specific CD8(+ )T lymphocytes were induced by the combined treatment, indicating that the control of tumor growth was most probably due to an immunological mechanism. The results demonstrated that doxorubicin and paclitaxel, commonly used chemotherapeutic agents for the treatment of breast cancer, when used at immunomodulating doses augmented the antitumor efficacy of gene vaccines directed against HER2/neu. CONCLUSIONS: The combination of chemotherapeutic agents plus vaccine immunotherapy may induce a tumor-specific immune response that could be beneficial for the adjuvant treatment of patients with minimal residual disease. The regimen warrants further evaluation in a clinical setting

Cardiovascular development: towards biomedical applicability: Epicardium-derived cells in cardiogenesis and cardiac regeneration

During cardiogenesis, the epicardium grows from the proepicardial organ to form the outermost layer of the early heart. Part of the epicardium undergoes epithelial-mesenchymal transformation, and migrates into the myocardium. These epicardium- derived cells differentiate into interstitial fibroblasts, coronary smooth muscle cells, and perivascular fibroblasts. Moreover, epicardium-derived cells are important regulators of formation of the compact myocardium, the coronary vasculature, and the Purkinje fiber network, thus being essential for proper cardiac development. The fibrous structures of the heart such as the fibrous heart skeleton and the semilunar and atrioventricular valves also depend on a contribution of these cells during development. We hypothesise that the essential properties of epicardium-derived cells can be recapitulated in adult diseased myocardium. These cells can therefore be considered as a novel source of adult stem cells useful in clinical cardiac regeneration therapy