Metastatic Gastric Signet Ring Cell Adenocarcinoma Masquerading as Low Back Pain.

This case report describes a 53-year-old Hispanic male who initially presented with acute hip pain. During workup, sclerotic bone lesions of the lumbar spine were identified on computed tomography (CT) in addition to extensive adenopathy involving the chest and abdomen. Upper endoscopy revealed chronic active gastritis, however, biopsies were negative for malignancy. Eventual bone marrow biopsy showed extensive infiltration by sheets of malignant epithelial cells with signet ring cell formation. Not only is this case significant for maintaining a broad differential in patients presenting with bone pain, but it also demonstrates a diagnosis of metastatic signet ring cell adenocarcinoma confirmed on bone marrow biopsy, which was not detected via earlier endoscopy.

Gastric Outlet Obstruction as the Initial Presentation of Upper Tract Urothelial Carcinoma.

GOO is often the first sign of advanced upper gastrointestinal neoplasms. The most common neoplasms associated with GOO include gastric, pancreatic, and biliary tract cancers. Urinary tract urothelial carcinoma has been a rarely documented cause of GOO.

N-Acetylcysteine in the Management of Acute Liver Failure From Sickle Cell Hepatic Crisis.

N-acetylcysteine (NAC) has been well studied in the treatment of acetaminophen-induced and select non-acetaminophen-induced liver failure. However, its role in the management of sickle cell hepatic crisis resulting in acute liver failure (ALF) is unknown. We describe and discuss the novel and beneficial use of NAC in a 25-year-old man with ALF due to sickle cell hepatic crisis. We further review ALF in sickle cell disease and NAC in the treatment of non-acetaminophen-induced liver failure. Our case highlights the promising role of NAC in sickle cell-related liver injury.

Arylboronic acid chemistry under electrospray conditions.

Boronic acids are important in the organic and biological arenas. Thus, their identification and characterization are important. ESI-MS is a well-known tool for such uses. Herein we report a systematic analysis of the chemical behavior of arylboronic acids under ESI-MS conditions. Such information will be very critical to understanding the gas-phase chemistry of boronic acids in an ESI mass spectrometer ion source in general and the MS analysis of boronic acids and their macromolecular conjugates in particular.

Hypoxia inducible factor pathway inhibitors as anticancer therapeutics.

Hypoxia is a significant feature of solid tumor cancers. Hypoxia leads to a more malignant phenotype that is resistant to chemotherapy and radiation, is more invasive and has greater metastatic potential. Hypoxia activates the hypoxia inducible factor (HIF) pathway, which mediates the biological effects of hypoxia in tissues. The HIF complex acts as a transcription factor for many genes that increase tumor survival and proliferation. To date, many HIF pathway inhibitors indirectly affect HIF but there have been no clinically approved direct HIF inhibitors. This can be attributed to the complexity of the HIF pathway, as well as to the challenges of inhibiting protein-protein interactions.

Binding Model for the Interaction of Anticancer Arylsulfonamides with the p300 Transcription Cofactor.

Hypoxia inducible factors (HIFs) are transcription factors that activate expression of multiple gene products and promote tumor adaptation to a hypoxic environment. To become transcriptionally active, HIFs associate with cofactors p300 or CBP. Previously, we found that arylsulfonamides can antagonize HIF transcription in a bioassay, block the p300/HIF-1α interaction, and exert potent anticancer activity in several animal models. In the present work, KCN1-bead affinity pull down, (14)C-labeled KCN1 binding, and KCN1-surface plasmon resonance measurements provide initial support for a mechanism in which KCN1 can bind to the CH1 domain of p300 and likely prevent the p300/HIF-1α assembly. Using a previously reported NMR structure of the p300/HIF-1α complex, we have identified potential binding sites in the p300-CH1 domain. A two-site binding model coupled with IC50 values has allowed establishment of a modest ROC-based enrichment and creation of a guide for future analogue synthesis.