Development and application of two novel monoclonal antibodies against overexpressed CD26 and integrin α3 in human pancreatic cancer.

Monoclonal antibody (mAb) technology is an excellent tool for the discovery of overexpressed cell surface tumour antigens and the development of targeting agents. Here, we report the development of two novel mAbs against CFPAC-1 human pancreatic cancer cells. Using ELISA, flow cytometry, immunoprecipitation, mass spectrometry, Western blot and immunohistochemistry, we found that the target antigens recognised by the two novel mAbs KU44.22B and KU44.13A, are integrin α3 and CD26 respectively, with high levels of expression in human pancreatic and other cancer cell lines and human pancreatic cancer tissue microarrays. Treatment with naked anti-CD26 mAb KU44.13A did not have any effect on the growth and migration of cancer cells nor did it induce receptor downregulation. In contrast, treatment with anti-integrin α3 mAb KU44.22B inhibited growth in vitro of Capan-2 cells, increased migration of BxPC-3 and CFPAC-1 cells and induced antibody internalisation. Both novel mAbs are capable of detecting their target antigens by immunohistochemistry but not by Western blot. These antibodies are excellent tools for studying the role of integrin α3 and CD26 in the complex biology of pancreatic cancer, their prognostic and predictive values and the therapeutic potential of their humanised and/or conjugated versions in patients whose tumours overexpress integrin α3 or CD26

Enhanced effect of checkpoint inhibitors when given after or together with IMM-101: significant responses in four advanced melanoma patients with no additional major toxicity

Background The use of checkpoint inhibitors (ipilimumab, pembrolizumab, nivolumab) has revolutionised the treatment of metastatic melanoma. However still more than the half the patients do not respond to single-agent immunotherapy. This has led to the development of combining these agents in an attempt to enhance the anti-cancer activity. More than 300 different studies with 15 different drug doses are currently ongoing. Combining different checkpoint inhibitors (CPIs) does indeed lead to an increase in response rate, but this is associated with significant toxicity. IMM-101 is a heat killed Mycobacterium preparation which induces marked immune modulation and little systemic toxicity. It has been reported as having activity in melanoma as single agent and in pancreatic cancer in combination with gemcitabine, the latter in a randomised study. Methods Here we report the effect of adding CPIs to 3 patients who had previously been on IMM-101, either as a trial or a named patient programme and a patient who received the IMM-101 together with nivolumab. Results All 4 patients had rapid and very good responses, three of them maintained over 18 months with no significant additional toxicity. Conclusions The rapid and complete clinical responses seen in these patients may suggest that IMM-101 is activating a complementary pathway which is synergistic with CPI treatment

Long-term Disease-free Survival Following Combination Multi-visceral and Metastatic Resection with Neoadjuvant FOLFIRINOX for Pancreatic Adenocarcinoma: A Case Report.

We describe a case of metastatic pancreatic adenocarcinoma treated with neoadjuvant FOLFIRINOX chemotherapy and combined pancreatic multi-visceral and metastatic liver resection in a patient currently disease-free four years after diagnosis

ニホンノチャエンニオケルチッソヒリョウケイタイガアサンカチッソハッセイトドジョウオヨビチャバノトクセイニアタエルエイキョウ

博士（農学）東京農工大

Lo Spazio dei problemi: processi di spazializzazione dei problemi sociali: il caso di Scampia

The issue of Italian popular suburbs has been the subject of specific investigations and urban policies. Policies aim to eliminate those problems that are considered more dramatic for these areas (crime, poverty, unemployment, school dropouts, etc.). At the same time, these policies seem to give rise to “priority geographies” in urban landscape. While both studies and the institutional framework are clearly addressed in some European contexts, such as France or England, in Italy there is a need to identify a proper approach. The goal of this research project is to understand if the Italian context of public policy is experiencing a creation process of priority geographies, through a spatialization of social problems. This subject will be investigated starting from an ethnographic field work within a “problematic” neighborhood in the north of Naples, called Scampia

Automated Dilated Spatio-Temporal Synchronous Graph Modeling for Traffic Prediction

Accurate traffic prediction is a challenging task in intelligent transportation systems because of the complex spatio-temporal dependencies in transportation networks. Many existing works utilize sophisticated temporal modeling approaches to incorporate with graph convolution networks (GCNs) for capturing short-term and long-term spatio-temporal dependencies. However, these separated modules with complicated designs could restrict effectiveness and efficiency of spatio-temporal representation learning. Furthermore, most previous works adopt the fixed graph construction methods to characterize the global spatio-temporal relations, which limits the learning capability of the model for different time periods and even different data scenarios. To overcome these limitations, we propose an automated dilated spatio-temporal synchronous graph network, named Auto-DSTSGN for traffic prediction. Specifically, we design an automated dilated spatio-temporal synchronous graph (Auto-DSTSG) module to capture the short-term and long-term spatio-temporal correlations by stacking deeper layers with dilation factors in an increasing order. Further, we propose a graph structure search approach to automatically construct the spatio-temporal synchronous graph that can adapt to different data scenarios. Extensive experiments on four real-world datasets demonstrate that our model can achieve about 10% improvements compared with the state-of-art methods. Source codes are available at https://github.com/jinguangyin/Auto-DSTSGN

Effects of Ferromagnetic & Carbon-Fibre Z-Pins on the Magnetic Properties of Composites

This paper investigates for the first time the effects of Z-pins on the magnetic properties of composite laminates. In-plane and out-of-plane M-H curves of IM7/8552 laminates with and without Z-pins have been characterised by an MPMS3 SQUID magnetometer. Two kinds of pin materials (T300/BMI composite and ferromagnetic Ni/Fe alloy) have been studied at three different volume fractions (nominally 0.5%, 2% and 4%). The unpinned and carbon-fibre pinned laminates were found to be diamagnetic. The carbon-fibre pin had no significant influence on the global magnetic properties of the laminates. The Ni/Fe alloy pin increased the laminate linear-part magnetic volume susceptibility up to 1.87 and 0.13 for the out-of-plane and in-plane directions, respectively. Numerical modelling has been conducted to support the investigation of the effect of the pin volume fraction on the overall magnetic susceptibility and saturation magnetisation. The laminate out-of-plane susceptibility exhibits a nonlinear behaviour dependent on pin volume fraction, due to interactions between adjacent pins. The saturation magnetisation is proportional to the pin volume fraction and independent of field direction