Extensive necrosis of visceral melanoma metastases after immunotherapy

<p>Abstract</p> <p>Background</p> <p>The prognosis for metastatic melanoma remains poor even with traditional decarbazine or interferon therapy. 5-year survival is markedly higher amongst patients undergoing metastatectomy. Unfortunately not all are suitable for metastatectomy. Alternative agents for systemic therapy have, to date, offered no greater rates of survival beyond traditional therapy. A toll-like receptor 9 agonist, PF-3512676 (formerly known as CPG 7909) is currently being evaluated for its potential.</p> <p>Case presentation</p> <p>We present the case of a 54-year-old Caucasian male with completely resected metastatic cutaneous melanoma after immunotherapy. The patient initially progressed during adjuvant high-dose interferon, with metastases to the liver, spleen, and pelvic lymph nodes. During an 18-month treatment period with PF-3512676 (formerly known as CPG 7909), a synthetic cytosine-phosphorothioate-guanine rich oligodeoxynucleotide, slow radiologic disease progression was demonstrated at the original disease sites. Subsequent excision of splenic and pelvic nodal metastases was performed, followed by resection of the liver metastases. Histologic examination of both hepatic and splenic melanoma metastases showed extensive necrosis. Subsequent disease-free status was demonstrated by serial positron emission tomography (PET).</p> <p>Conclusion</p> <p>Existing evidence from phase I/II trials suggests systemic treatment with PF-3512676 is capable of provoking a strong tumor-specific immune response and may account for the prolonged tumor control in this instance.</p

Highly active and efficient catalysts for alkoxycarbonylation of alkenes

Carbonylation reactions of alkenes constitute the most important industrial processes in homogeneous catalysis. Despite the tremendous progress in this transformation, the development of advanced catalyst systems to improve their activity and widen the range of feedstocks continues to be essential for new practical applications. Herein a palladium catalyst based on 1,2-bis((tert-butyl(pyridin-2-yl)phosphanyl)methyl)benzene L3 (py(t)bpx) is rationally designed and synthesized. Application of this system allows a general alkoxycarbonylation of sterically hindered and demanding olefins including all kinds of tetra-, tri- and 1,1-disubstituted alkenes as well as natural products and pharmaceuticals to the desired esters in excellent yield. Industrially relevant bulk ethylene is functionalized with high activity (TON: >1,425,000; TOF: 44,000 h(−1) for initial 18 h) and selectivity (>99%). Given its generality and efficiency, we expect this catalytic system to immediately impact both the chemical industry and research laboratories by providing a practical synthetic tool for the transformation of nearly any alkene into a versatile ester product

Letter to Nature: A dark jet dominates the power output of the stellar black hole Cygnus X-1

Black holes undergoing accretion are thought to emit the bulk of their power in the X-ray band by releasing the gravitational potential energy of the infalling matter1. At the same time, they are capable of producing highly collimated jets of energy and particles flowing out of the system with relativistic velocities2. Here we show that the 10-solar-mass (10M☉) black hole in the X-ray binary Cygnus X-1 (refs 3–5) is surrounded by a large-scale (~5 pc in diameter) ring-like structure that appears to be inflated by the inner radio jet6. We estimate that in order to sustain the observed emission of the ring, the jet of Cygnus X-1 has to carry a kinetic power that can be as high as the bolometric X-ray luminosity of the binary system. This result may imply that low-luminosity stellar-mass black holes as a whole dissipate the bulk of the liberated accretion power in the form of 'dark', radiatively inefficient relativistic outflows, rather than locally in the X-ray-emitting inflow

A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci

10.1038/ng.601Nature Genetics427599-60