It has previously been demonstrated that phenanthroline-based ligands used to make gold metallotherapuetics have the ability to exhibit cytotoxicity when not coordinated to the metal center. In an effort to help assess the mechanism by which these ligands may cause tumor cell death, iron binding and removal experiments have been considered. The close linkage between cell proliferation and intracellular iron concentrations suggest that iron deprivation strategies may be a mechanism involved in inhibiting tumor cell growth. With the creation of iron (III) phen complexes, the iron binding abilities of three polypyridal ligands [1,10-phenanthroline (phen), 2,9-dimethyl-1, 10-phenanthroline (methylphen), and 2,9-di-sec-butyl-1, 10-phenanthroline (sec-butylphen)] can be tested via a competition reaction with a known iron chelator. Therefore, iron (III) complexes possessing all three ligands were synthesized. Initial mass spectrometric and infrared absorption data indicate that iron (III) tetrachloride complex ions with protonated phen ligands (RphenH+) were formed: [phenH][FeCl4], [methylphenH][FeCl4], [sec-butylphenH][FeCl4]. UV-Vis spectroscopy was used to monitor the stability of the complex ions, and it was found that the sec-butylpheniron complex was more stable than the phen and methylphen analogues. This was based on the observation that free ligand was observed immediately upon the addition of EDTA to the [phenH][FeCl4] and [methylphenH] [FeCl4] complex ions.

Introduction Clinical indications of immune checkpoint inhibitors have expanded to a variety of malignancies. Approximately one in six patients with hepatocellular carcinoma respond to programmed death 1 inhibitors nivolumab and pembrolizumab. Case report We report herein a patient with synchronous metastatic hepatocellular carcinoma and advanced papillary thyroid carcinoma treated with nivolumab in the second-line therapy. Management and outcome: The hepatocellular carcinoma showed a durable response to the second-line agent nivolumab. Remarkably, the patient’s papillary thyroid carcinoma also responded to this programmed death 1 inhibitor. Discussion To our knowledge, this is the first case report showing the efficacy of nivolumab in the treatment of metastatic papillary thyroid carcinoma. Further studies with immune checkpoint inhibitors in papillary thyroid carcinoma seem warranted.

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Magnocellular neuroendocrine cells (MNCs) in the supraoptic (SON) and paraventricular nucleus (PVN) of the hypothalamus release vasopressin (VP) from axons and somata/dendrites in response to hyperosmotic stimulation. Transient receptor potential vanilloid 1 (TRPV1) channels mediate osmosensory transduction and axonal neurosecretion in SON MNCs. Our lab has shown that osmotic‐stimulated somatodendritic VP responses occur in a TRPV1‐ and NOS‐dependent manner. Since TRPV1 activation may result in NO production, our current study examined the interaction between TRPV1 and NO synthase (NOS) under hyperosmotic conditions. Acutely dissected SON slices were prepared from adult male Holtzman rats perfused with sucrose‐enriched aCSF under deep anesthesia. Slices were treated with hyperosmotic stimulation in the presence and absence of TRPV1 antagonist SB366791 (1.5 μM) and later post‐fixed. Using double‐label immunohistochemistry for phosphorylated stimulatory residue of neuronal NOS (p‐nNOS ser1412) and combined VP‐neurophysin (PS41) and oxytocin‐neurophysin (PS38) we found elevated p‐nNOS immunoreactivity in MNCs under hyperosmotic conditions but not always in the presence of SB366791, suggesting that increased NO signaling may occur downstream of TRPV1 channel activity. By analogy to other neuroendocrine systems p‐nNOS ser1412 may participate in neuropeptide secretion perhaps by coupling with NMDAr on MNCs. We also immunoprobed for downstream signaling partners of NOS and found expression of sGC (beta subunit), an enzyme that converts GTP to cGMP. We conclude that hyperosmotic stimulation activates TRPV1 channels that produce stimulatory phosphorylation of nNOS leading to somatodendritic release of VP from supraoptic MNCs. Grant Funding Source: Supported by American Physiological Society