Probable interaction between Lycium barbarum (goji) and warfarin.

Lycium barbarum (also called goji berry), a Chinese herb used as a supplement for health benefits, is traditionally consumed by the Chinese in the form of a tea. Goji juice, a widely available beverage in the United States, also contains this herb. We describe a 71-year-old Ecuadorean-American woman who was taking warfarin and was hospitalized for a markedly elevated, indeterminate international normalized ratio (INR) (prothrombin time > 120 sec) after consumption of goji juice. She had undergone knee surgery approximately 3 months earlier at which time warfarin therapy was started. She reported no changes in dietary habits or lifestyle other than drinking goji juice for 4 days before hospitalization. On presentation to the emergency department, she described symptoms of epistaxis, bruising, and rectal bleeding. After discontinuation of the goji juice and warfarin, the patient was treated with phytonadione, and her INR decreased to 2.6 over 2 days. Application of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patient's elevated INR with associated bleeding and her concomitant use of L. barbarum and warfarin. Two other published reports have described similar interactions between warfarin and a tea containing L. barbarum. Patients should be educated about avoiding popular herbal drinks, such as goji juice, that contain L. barbarum while they are taking warfarin. In addition, clinicians should question patients about their use of herbal therapies and document such use in their medical records before prescribing drugs such as warfarin.

Gastrin-releasing peptide signaling alters colon cancer invasiveness via heterochromatin protein 1Hsß.

Epithelial cells lining the adult colon do not normally express gastrin-releasing peptide (GRP) or its receptor (GRPR). In contrast, GRP/GRPR can be aberrantly expressed in colon cancer where they are associated with improved patient survival rates. However, the mechanism of action whereby these proteins mediate their beneficial effects is not known. Heterochromatin protein 1 is an epigenetic modifier of gene transcription for which three different isoforms exist in humans: HP1(Hsα), HP1(Hsß), and HP1(Hsγ). In breast cancer and melanoma, respectively, HP1(Hsα) and HP1(Hsß) have been shown to modulate the aggressiveness of tumor cells in vivo. In contrast, the role of HP1 in colon cancer has not been elucidated, and a mechanism of regulating the expression of any HP1 isoform in any context has not yet been identified. In this article we demonstrate that abrogating GRP/GRPR signaling specifically down-regulates HP1(Hsß) expression and that inhibiting GRPR signaling, or ablating HP1(Hsß) expression, increases colon cancer cell invasiveness in vitro. These findings identify for the first time a signaling pathway regulating heterochromatin protein expression and suggest a mechanism whereby aberrantly expressed GRPR might alter the outcome of patients with colorectal cancer.

Expression of GRP and its receptor is associated with improved survival in patients with colon cancer.

Epithelial cells lining the adult human colon do not normally express gastrin releasing peptide (GRP) or its receptor (GRPR), but both can be up regulated post malignant transformation. However, controversy exists as to the contribution these proteins make to tumor cell behavior once present. Since GRPR activation promotes proliferation, it has been assumed that their aberrant expression promotes colon cancer (CC) growth and progression. Yet we have contended that when expressed, GRP/GRPR benefits the host since in vitro studies demonstrate they enhance tumor cell attachment to the extracellular matrix and promote CC cytolysis by natural killer lymphocytes. Thus the aim of this study was to ascertain the effect of aberrant GRP/GRPR expression on patient survival. To do this we identified all CC diagnosed at a single institution from 1998 to 2002 that were classified as AJCC stage II or III (n = 88); of these 50 (57%) had sufficient tissues remaining for study. GRP/GRPR expression and natural killer cell density were determined immunohistochemically at the leading edge of each CC, and survival assessed by Kaplan Meier analysis. Expression of high levels of GRPR alone, or both GRP and GRPR, was associated with delayed CC recurrence (14.1-17.0 months, respectfully; P = 0.005) and increased survival (10.1-13.1 months, respectfully; P = 0.0124). CC expressing GRP/GRPR were associated with significantly fewer lymph node metastases than tumors not expressing these proteins, and contained significantly more CD16 + natural killer cells, than tumors not expressing these proteins. These findings demonstrate that patients whose CC express GRPR are associated with a survival advantage as compared to those whose CC do not express these proteins.