Carfilzomib-lenalidomide-dexamethasone therapy is tolerable and demonstrates high rates of MRD negativity in NDMM, translating into longer progression-free survival in patients achieving MRD negativity. Carfilzomib-lenalidomide-dexamethasone therapy also demonstrates efficacy in high-risk SMM.

No abstract

High-risk cutaneous squamous cell carcinoma (SCC) is associated with an increased risk of metastases. The role of sentinel lymph node (SLN) biopsy in these patients remains unclear. To address this uncertainty, we collected clinical data on six patients with clinical N0 high-risk SCC that underwent SLN biopsy between 1999 and 2006 and performed a literature review of SLN procedures for SCC to study the utility of SLN biopsy. There were no positive SLN identified among six cases and there was one local and one distant recurrence on follow-up. Literature review identified 130 reported cases of SLN biopsy for SCC. The SLN positivity rate was 14.1%, 10.1%, and 18.6%; false negative rate was 15.4%, 0%, and 22.2%; and the negative predictive value was 97.8%, 100%, and 95.2% for all sites, head/neck, and truncal/extremity sites, respectively. SLN biopsy remains an investigational staging tool in clinically node-negative high-risk SCC patients. The higher false negative rate and lower negative predictive value among SCC of the trunk/extremity compared to SCC of the head/neck sites suggests a more cautious approach when treating patients with the former. Given the paucity of long-term follow up, an emphasis is placed upon the need for close surveillance regardless of SLN status.

Since the early 1990s, the synthesis and subsequent clinical application of small molecule inhibitors of the ubiquitin proteasome pathway (UPP) has revolutionized the treatment and prognosis of multiple myeloma. In this review, we summarize important aspects of the biology of the UPP with a focus on its structure and key upstream/downstream regulatory components. We then review current knowledge of plasma cell sensitivity to proteasome inhibition and highlight new proteasome inhibitors that have recently entered clinical development. Lastly, we address the putative role of circulating proteasomes as a novel biomarker in multiple myeloma and provide guidance for future clinical trials using proteasome inhibitors.

Quick and clean: Excellent protein yields in cell‐free protein synthesis can be obtained by using polymerase chain reaction (PCR) amplified DNA templates, provided that the templates are designed for cyclization. This eliminates time‐consuming cloning steps and allows one to go from complementary DNA to the protein NMR spectrum in 24 h.

No abstract

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an adaptor protein composed of two homophilic protein-protein interaction domains, a PYRIN domain (PYD) and a caspase recruitment domain. PYD-dependent oligomerization of ASC is thought to play a crucial role in formation of a molecular platform, the inflammasome, which activates caspase-1. When expressed in cells, the PYD of ASC was shown to form cytoplasmic filaments through self-association. Over 70 single point mutants were analyzed for filament formation in cells expressing the mutant proteins. The set of mutations comprised every single amino acid residue with a charged side chain (Arg, Lys, Asp, and Glu) and a large hydrophobic side chain (Ile, Leu, Met, Phe, Pro, and Val). Filament formation of the ASC PYD was prevented by mutation of Lys21, Leu25, Lys26, Pro40, Arg41, Asp48, and Asp51 of helices 2, 3, and 4. These data identify a coherent interaction surface, establishing a molecular model of PYD-PYD complexes with an important role for charge-charge interactions.

CHPP with cisplatin can be performed safely with no mortality and minimal morbidity. In selected patients, successful palliation in the abdomen and long-term survival, compared with historical controls, can be achieved with aggressive surgical debulking and CHPP. Re-treatment after initial response can result in a second long-term response.