Insulin-like growth factors and insulin control a multifunctional signalling network of significant importance in cancer

Insulin-like growth factor (IGF) and insulin (INS) proteins regulate key cellular functions through a complex interacting multi-component molecular network, known as the IGF/INS axis. We describe how dynamic and multilayer interactions give rise to the multifunctional role of the IGF/INS axis. Furthermore, we summarise the importance of the regulatory IGF/INS network in cancer, and discuss the possibilities and limitations of therapies targeting the IGF/INS axis with reference to ongoing clinical trials concerning the blockage of IGF1R in several types of cancer

Minimum breast distance largely explains individual variability in doses to contralateral breast from breast-cancer radiotherapy.

Purpose: To provide personalized estimates of doses to contralateral breast (CB) from breast-cancer radiotherapy.Methods: Whole-breast irradiations using 3D conformal, intensity-modulated and hybrid techniques with 50.4 Gy prescribed dose were planned for 128 breast-cancer patients. From their CT images, 17 anatomic measures were assessed and tested by model fitting as predictors for CB dose-volume characteristics.Results: Multi-field intensity-modulated radiotherapy (IMRT) yielded mean CB doses of 0.8-7.1 Gy, with no correlation to the studied anatomic parameters. Tangential whole-breast irradiation led to much lower mean CB doses, 0.2-1.6 Gy. About 60% of this inter-patient variability was explained by individual variations in a single anatomic measure, the minimum breast distance (MBD), defined as the CB distance from the tangent to the treated breast. Per 1 cm increase in MBD, the mean CB dose decreased by 10-15%. As an alternative to MBD, dose estimates could be based on the breast-to-breast distance, which is highly correlated with MBD.Conclusion: The results enable personalized assessment of CB doses from tangential whole-breast irradiation, based only on parameters assessable from CT data. This may help support clinical decision-making processes as well as analyse retrospective studies on CB risks. (C) 2018 Elsevier B.V. All rights reserved

Micro welding of aluminum for post process electrode gap reduction using femtosecond laser

This paper presents a new technology, which allows the reduction of the micro dimensional trench width below the technological limitations of the Deep Reactive Ion Etching (DRIE) process. The high-accuracy and high-throughput femtosecond laser-micro-welding of aluminum was performed for the first time by Micro Electrical Mechanical System (MEMS) fabrication to realize this permanent trench width reduction. Therefore, this technology has been applied for the electrode gap reduction of high precision vibration sensors, based on the capacitive working principle, resulting in a fourfold improvement of the sensitivity without changing the size of the sensor chip itself

What anatomic features govern personal long-term health risks from breast cancer radiotherapy?

Breast cancer radiotherapy may in the long term lead to radiation-induced secondary cancer or heart disease. These health risks hugely vary among patients, partially due to anatomy-driven differences in doses deposited to the heart, ipsilateral lung and contralateral breast. We identify four anatomic features that largely cover these dosimetric variations to enable personalized risk estimates. For three exemplary, very different risk scenarios, the given parameter set reproduces 63-74% of the individual risk variability for left-sided breast cancer patients. These anatomic features will be used in the PASSOS software to support decision processes in breast-cancer therapy

Inter-patient variability in doses to nearby organs in breast-cancer radiotherapy: Inference from anatomic features.

With improved cure rates and prolonged patient survival after breast-cancer radiotherapy, radiation-induced second cancers and heart diseases become increasingly important. The heart, lungs and contralateral breast are the most critical organs for these long-term effects. Doses to these organs and hence the risks differ between radiotherapy techniques and especially among patients. To address this variability, treatment plans were generated for 128 early-stage breast-cancer patients using intensity-modulated, 3D-conformal and hybrid radiotherapy. Twenty dedicated anatomic measures were assessed from CT data, such as the width and thickness of the treated breast or its distance from the heart. Their impact on doses to critical nearby organs was analysed. The majority of inter-patient variability can be covered with a few anatomic parameters. Patients can thus be stratified according to long-term risks already before treatment planning, and guidance can be provided towards a personalised selection of technique associated with the lowest risk

Exposure of remote organs and associated cancer risks from tangential and multi-field breast cancer radiotherapy.

PurposeWith the ever-increasing cure rates in breast cancer, radiotherapy-induced cancers have become an important issue. This study aimed to estimate secondary cancer risks for different treatment techniques, taking into account organs throughout the body.Material and methodsOrgan doses were evaluated for atangential three-dimensional conformal (3D-CRT) and amulti-field intensity-modulated radiotherapy (IMRT) plan using avalidated, Monte Carlo-based treatment planning system. Effects of wedges and of forward versus inverse planning were systematically investigated on the basis of phantom measurements. Organ-specific cancer risks were estimated using risk coefficients derived from radiotherapy patients or from the atomic bomb survivors.ResultsIn the 3D-CRT plan, mean organ doses could be kept below 1Gy for more remote organs than the lung, heart, and contralateral breast, and decreased to afew cGy for organs in the lower torso. Multi-field IMRT led to considerably higher mean doses in organs at risk, the difference being higher than 50% for many organs. Likewise, the peripheral radiation burden was increased by external wedges. No difference was observed for forward versus inverse planning. Despite the lower doses, the total estimated secondary cancer risk in more remote organs was comparable to that in the lung or the contralateral breast. For multi-field IMRT it was 75% higher than for 3D-CRT without external wedges.ConclusionRemote organs are important for assessment of radiation-induced cancer risk. Remote doses can be reduced effectively by application of atangential field configuration and alinear accelerator set-up with low head scatter radiation