Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer

So far, the therapeutic outcome of hyperthermia has shown heterogeneous responses depending on how thermal stress is applied. We studied whether extrinsic heating (EH, hot air) and intrinsic heating (magnetic heating [MH] mediated by nanoparticles) induce distinct effects on pancreatic cancer cells (PANC-1 and BxPC-3 cells). The impact of MH (100 µg magnetic nanoparticles [MNP]/mL; H=23.9 kA/m; f=410 kHz) was always superior to that of EH. The thermal effects were confirmed by the following observations: 1) decreased number of vital cells, 2) altered expression of pro-caspases, and 3) production of reactive oxygen species, and 4) altered mRNA expression of Ki-67, TOP2A, and TPX2. The MH treatment of tumor xenografts significantly (P≤0.05) reduced tumor volumes. This means that different therapeutic outcomes of hyperthermia are related to the different responses cells exert to thermal stress. In particular, intratumoral MH is a valuable tool for the treatment of pancreatic cancers

Extreme events in time series aggregation: A case study for optimal residential energy supply systems

To account for volatile renewable energy supply, energy systems optimization problems require high temporal resolution. Many models use time-series clustering to find representative periods to reduce the amount of time-series input data and make the optimization problem computationally tractable. However, clustering methods remove peaks and other extreme events, which are important to achieve robust system designs. We present a general decision framework to include extreme events in a set of representative periods. We introduce a method to find extreme periods based on the slack variables of the optimization problem itself. Our method is evaluated and benchmarked with other extreme period inclusion methods from the literature for a design and operations optimization problem: a residential energy supply system. Our method ensures feasibility over the full input data of the residential energy supply system although the design optimization is performed on the reduced data set. We show that using extreme periods as part of representative periods improves the accuracy of the optimization results by 3% to more than 75% depending on system constraints compared to results with clustering only, and thus reduces system cost and enhances system reliability

Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients

The incidence of oral squamous cell carcinoma remains high. Oral and oro-pharyngeal carcinomas are the sixth most common cancer in the world. Several clinicopathological parameters have been implicated in prognosis, recurrence and survival, following oral squamous cell carcinoma. In this retrospective analysis, clinicopathological parameters of 115 T1/T2 OSCC were studied and compared to recurrence and death from tumour-related causes. The study protocol was approved by the Joint UCL/UCLH committees of the ethics for human research. The patients' data was entered onto proformas, which were validated and checked by interval sampling. The fields included a range of clinical, operative and histopathological variables related to the status of the surgical margins. Data collection also included recurrence, cause of death, date of death and last clinic review. Causes of death were collated in 4 categories (1) death from locoregional spread, (2) death from distant metastasis, (3) death from bronchopulmonary pneumonia, and (4) death from any non-tumour event that lead to cardiorespiratory failure. The patients' population comprised 65 males and 50 females. Their mean age at the 1 diagnosis of OSCC was 61.7 years. Two-thirds of the patients were Caucasians. Primary sites were mainly identified in the tongue, floor of mouth (FOM), buccal mucosa and alveolus. Most of the identified OSCCs were low-risk (T1N0 and T2N0). All patients underwent primary resection neck dissection and reconstruction when necessary. Twenty-two patients needed adjuvant radiotherapy. Pathological analysis revealed that half of the patients had moderately differentiated OSCC. pTNM slightly differed from the cTNM and showed that 70.4% of the patients had low-risk OSCC. Tumour clearance was ultimately achieved in 107 patients. Follow-up resulted in a 3-year survival of 74.8% and a 5-year survival of 72.2%. Recurrence was identified in 23 males and 20 females. The mean age of 1 diagnosis of the recurrence group was 59.53 years. Most common oral sites included the lateral border of tongue and floor of mouth. Recurrence was associated with clinical N-stage disease. The surgical margins in this group was evaluated and found that 17 had non-cohesive invasion, 30 had dysplasia at margin, 21 had vascular invasion, 9 had nerve invasion and 3 had bony invasion. Severe dysplasia was present in 37 patients. Tumour clearance was achieved in only 8 patients. The mean depth of tumour invasion in the recurrence group was 7.6 mm. An interesting finding was that 5/11 patients who died of distant metastasis had their primary disease in the tongue. Nodal disease comparison showed that 8/10 patients who died of locoregional metastasis and 8/11 patients who died from distant metastasis had clinical nodal involvement. Comparing this to pathological nodal disease (pTNM) showed that 10/10 patients and 10/11 patients who died from locoregional and distant metastasis, respectively, had nodal disease. All patients who died from locoregional and distant metastasis were shown to have recurrence after the primary tumour resection. Squamous cell carcinoma of the oral cavity has a poor overall prognosis with a high tendency to recur at the primary site and extend to involve the cervical lymph nodes. Several clinicopathological parameters can be employed to assess outcome, recurrence and overall survival. © 2010 Jerjes et al; licensee BioMed Central Ltd

Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer

Robert Ludwig,1 Francisco J Teran,2,3 Ulf Teichgraeber,1 Ingrid Hilger1 1Department of Experimental Radiology, Institute for Diagnostic and Interventional Radiology, Jena University Hospital – Friedrich Schiller University Jena, Jena, Germany; 2iMdea-Nanociencia, Campus Universitario de Cantoblanco, 3Nanobiotecnología (iMdea-Nanociencia), Unidad Asociada al Centro Nacional de Biotecnología (CSIC), Madrid, Spain Abstract: So far, the therapeutic outcome of hyperthermia has shown heterogeneous responses depending on how thermal stress is applied. We studied whether extrinsic heating (EH, hot air) and intrinsic heating (magnetic heating [MH] mediated by nanoparticles) induce distinct effects on pancreatic cancer cells (PANC-1 and BxPC-3 cells). The impact of MH (100 µg magnetic nanoparticles [MNP]/mL; H=23.9 kA/m; f=410 kHz) was always superior to that of EH. The thermal effects were confirmed by the following observations: 1) decreased number of vital cells, 2) altered expression of pro-caspases, and 3) production of reactive oxygen species, and 4) altered mRNA expression of Ki-67, TOP2A, and TPX2. The MH treatment of tumor xenografts significantly (P≤0.05) reduced tumor volumes. This means that different therapeutic outcomes of hyperthermia are related to the different responses cells exert to thermal stress. In particular, intratumoral MH is a valuable tool for the treatment of pancreatic cancers. Keywords: iron oxide nanoparticles, magnetic hyperthermia, heat dose, nanomedicine, proliferation marke

Anatomical variations in the internal jugular veins of cancer patients affecting central venous access. Anatomical variation of the internal jugular vein

Purpose: Establishing a reliable central venous access is an important procedure in clinical haematology and oncology. The purpose of this study was to determine how anatomical variations in the internal jugular vein (IJV) and its position in relation to the common carotid artery (CCA) in cancer patients affects external landmark puncture. Patients and Methods: In 113 patients with haematological or oncological diseases we examined sonographically potential target regions for placement of a central catheter via the IJV. Results: 36 % of our patients showed anatomical variations in the IJV and surrounding tissue. Conclusions: External landmark puncture may be difficult in a considerable number of patients since the IJV might not be situated in the presumed location anteriorly or laterally to the CCA, or a normal lumen may not be present in approximately ⅓ of cancer patients. This study supports the use of ultrasound-guided techniques for central venous catheters particularly in haematological and oncological patients