Combination of Lenvatinib and Pembrolizumab Is an Effective Treatment Option for Anaplastic and Poorly Differentiated Thyroid Carcinoma.

Background: Anaplastic thyroid carcinoma (ATC) and metastatic poorly differentiated thyroid carcinomas (PDTCs) are rare aggressive malignancies with poor overall survival (OS) despite extensive multimodal therapy. These tumors are highly proliferative, with frequently increased tumor mutational burden (TMB) compared with differentiated thyroid carcinomas, and elevated programmed death ligand 1 (PD-L1) levels. These tumor properties implicate responsiveness to antiangiogenic and antiproliferative multikinase inhibitors such as lenvatinib, and immune checkpoint inhibitors such as pembrolizumab. Patients and Methods: In a retrospective study, we analyzed six patients with metastatic ATC and two patients with PDTC, who received a combination therapy of lenvatinib and pembrolizumab. Lenvatinib was started at 14-24 mg daily and combined with pembrolizumab at a fixed dose of 200 mg every three weeks. Maximum treatment duration with this combination was 40 months, and 3 of 6 ATC patients are still on therapy. Patient tumors were characterized by whole-exome sequencing and PD-L1 expression levels (tumor proportion score [TPS] 1-90%). Results: Best overall response (BOR) within ATCs was 66% complete remissions (4/6 CR), 16% stable disease (1/6 SD), and 16% progressive disease (1/6 PD). BOR within PDTCs was partial remission (PR 2/2). The median progression-free survival was 17.75 months for all patients, and 16.5 months for ATCs, with treatment durations ranging from 1 to 40 months (1, 4, 11, 15, 19, 25, 27, and 40 months). Grade III/IV toxicities developed in 4 of 8 patients, requiring dose reduction/discontinuation of lenvatinib. The median OS was 18.5 months, with three ATC patients being still alive without relapse (40, 27, and 19 months) despite metastatic disease at the time of treatment initiation (UICC and stage IVC). All patients with long-term (>2 years) or complete responses (CRs) had either increased TMB or a PD-L1 TPS >50%. Conclusions: Our results implicate that the combination of lenvatinib and pembrolizumab might be safe and effective in patients with ATC/PDTC and can result in complete and long-term remissions. The combination treatment is now being systematically examined in a phase II clinical trial (Anaplastic Thyroid Carcinoma Lenvatinib Pembrolizumab [ATLEP]) in ATC/PDTC patients.

Synthesis of multiantennary complex type N-glycans by use of modular building blocks.

A modular set of oligosaccharide building blocks was developed for the synthesis of multiantennary N-glycans of the complex type, which are commonly found on glycoproteins. The donor building blocks were laid out for the elongation of a core trisaccharide acceptor (beta-mannosyl chitobiose) conveniently protected with a single benzylidene moiety at the beta-mannoside. Through two consecutive regio- and stereoselective couplings the donors gave N-glycans with three to five antennae in high yields. Due to the consistent protection group pattern of the donors the deprotection of the final products can be performed by using a general reaction sequence.

[Granulomatous dermatitis following herpes zoster with detection of varicella zoster virus DNA]. / Postzosterische granulomatöse Dermatitis mit Nachweis von Varizella-Zoster-Virus-DNA.

The occurrence of a granulomatous inflammation following herpes zoster infection is uncommon and its pathogenesis is unclear. A 74-year-old male patient developed multiple red-brown papules following a secondary generalized infection with varicella zoster virus in the same area. The patient was suffering from a chronic lymphocytic B-cell leukaemia. Histopathologically, granulomatous dermatitis with multinucleate giant cells was found. Varicella zoster virus DNA was identified by polymerase chain reaction in the tissue. After a renewed antiviral therapy, skin lesions disappeared completely.

Semiconductor photocatalysis type B: synthesis of unsaturated alpha-amino esters from imines and olefins photocatalyzed by silica-supported cadmium sulfide.

Novel unsaturated N-phenyl-alpha-amino esters were synthesized in isolated yields of 50 to 10% by visible light irradiation of methanolic suspensions of silica-supported cadmium sulfide in the presence of methyl (2Z)-phenyl(phenylimino)acetate and various cyclic olefins. A semiconductor photocatalysis mechanism is proposed for this linear addition reaction. The light-generated electron-hole pair in the oxidative step induces a dissociative electron transfer from the olefin to CdS affording a proton and an allylic radical, whereas in the reductive step an alpha-aminobenzyl radical is formed in a proton coupled reaction. Heterocoupling of these intermediate radicals leads to the corresponding addition products. As the only by-product the hydrogenated imine is obtained in comparable amounts through the subsequent photoreduction of the alpha-aminobenzyl radical. Supporting the catalyst on silica made the reaction three times faster as compared to neat CdS. When the surface OH groups of CdS were removed through alkylation, the reaction between ArCH=NAr (Ar = p-C1C6H4) and cyclopentene was completely inhibited, but occurred again upon replacing the aldimine by its hydrochloride salt. This indicates that the protonated aldimine is involved in the reductive reaction step. Protonation makes this reduction easier by 0.1 V as indicated by the shift of the reduction potential of methyl (2Z)-phenyl(phenylimino)acetate upon addition of glacial acetic acid to the acetonitrile solution.

Electronic Semiconductor-Support Interaction-A Novel Effect in Semiconductor Photocatalysis.

The bandgap of CdS increases with decreasing coverage when CdS is supported on silica (see plot of Ebg against CdS concentration c). Likewise the photocatalytic activity of these heterogeneous photocatalysts increases, as illustrated by the relative rate (vrel ) of an organic addition reaction. CdS (A, vrel =1), CdS-50/SiO2 (B), CdS-30/SiO2 (C), and CdS-12/SiO2 (D).