The Tumor and its Microenvironment in Mesothelioma

__Abstract__ Asbestos is a natural mineral that was, and unfortunately still is, used a lot by mankind because of the outstanding properties of the substance. It is durable, strong, electricand heat-resistant and, last but not least, cheap. The discovery of these properties was made millennia ago in ancient Greek, and thus the mining and use of asbestos was initiated over 2000 years ago. During the middle ages, the use of asbestos declined, but in the documents remaining, several descriptions of asbestos use were described. For example, Charlemagne (2 April 747 or 748 – 28 January 814) convinced his guests that he had supernatural powers by throwing his asbestos tablecloth into a fire, and then pulling it out without any singe mark of burning1. Marco Polo wore fire-resistant clothing made from fibrous material on his travels in the Ural Mountains in the 13th century1. The popularity of the material clearly increased in the 19th century, when asbestos was massively used during the industrial revolution. It further increased in the 20th century; a total of 174 million tons of asbestos was mined during these 100 years2. Despite asbestos bans in a growing number of countries worldwide, in the year 2013, a total of 1.94 million tons of asbestos was mined3. In the Netherlands, the population mainly

Thymoma and Thymic Carcinoma

Malignancies of the thymus are a rare entity and are often without local symptoms. However, paraneoplastic syndromes can give symptoms varying from very mild to life-threatening. The diagnostic workup and management of these tumors warrant a multidisciplinary approach. Treatment choice is mainly decided upon by pathological World Health Organization (WHO) subtype and clinical staging. In contrast to historical belief, biopsy could be considered when indicated. For resectable tumors, surgical approach is advised, with adjuvant radiotherapy for Masaoka-Koga stage III tumors. Whether Masaoka-Koga stage II tumors should be treated with radiotherapy is controversial given different outcomes in multiple studies. In Masaoka-Koga stage III, combinations with induction chemotherapy are the standard. A surgical approach should be considered even in stage IVa disease. If distant metastases are present, the patient can be treated with systemic chemotherapy. Despite many phase II studies having been published, there is no randomized controlled phase III data regarding optimal treatment available. In addition to chemotherapy, sunitinib and octreotide have been described to be effective. Immunotherapy is seen as Pandora’s box given the possibility of immune-related side effects in this immunological organ. All known data regarding immunotherapy will be discussed

Protecting Encapsulin Nanoparticles with Cysteine-Knot Miniproteins

A big hurdle for the use of protein-based drugs is that they are easily degraded by proteases in the human body. In an attempt to solve this problem, we show the possibility to functionalize TM encapsulin nanoparticles with an mEETI-II knottin miniprotein from the cysteine-stabilized knot class. The resulting particles did not show aggregation and retained part of their protease inhibitive function. This imposes a protection toward protease, in this case, trypsin, degradation of the protein cage. The used chemistry is easy to apply and thus suitable to protect other protein systems from degradation. In addition, this proof of principle opens up the use of other knottins or cysteine-stabilized knots, which can be attached to protein cages to create a heterofunctionalized protein nanocage. This allows specific targeting and tumor suppression among other types of functionalization. Overall, this is a promising strategy to protect a protein of interest which brings oral administration of protein-based drugs one step closer.</p