Although exogenous porphyrin accumulation in cancer cells is important for the success of photodynamic therapies, the mechanism is not clear. We hypothesized that a newly reported transporter, heme carrier protein 1 (HCP1), is highly expressed in cancer cells, and transports porphyrins into the cells. We investigated the following three unknowns: whether cancer cells take up hematoporphyrin derivative via HCP1, whether HCP1 is involved in photodynamic therapies, and whether cancer cells highly express HCP1. First, when HCP1-overexpressed cells were treated with hematoporphyrin derivative and then exposed to an eximer laser beam, they emitted a significantly higher intensity of hematoporphyrin derivative fluorescence and became more susceptible to the laser beam than control. Second, when three other types of cancer cells with silenced HCP1 were treated with hematoporphyrin derivative and then exposed to the laser beam, they emitted a significantly lower intensity of hematoporphyrin derivative fluorescence. Third, non-cancer cells slightly expressed HCP1; on the other hand, the three other types of cancer cells clearly expressed HCP1. These results indicated that cancer cells uptake hematoporphyrin derivative via HCP1 and over-expression of HCP1 increases the efficacy of photodynamic therapies by increasing porphyrin accumulation in the cells. This is the first report about a transporter of porphyrin in cancer cells.

Key Clinical MessageWe need to be aware of primary intestinal lymphoproliferative disease (PILD) associated with ulcerative colitis (UC). We should carefully monitor UC patients, particularly patients who meet the following conditions; a previous Epstein-Barr virus infection, treatment duration ≧4 years, male, and age ≧50 years.

Key Clinical MessagePolyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes (POEMS) syndrome is a rare plasma cell disorder that causes a paraneoplastic syndrome. We report the first case of POEMS syndrome with synchronous breast cancer. The patient was at risk of being misdiagnosed with metastatic cancer, and it is important to emphasize that physical examinations provided vital diagnostic clues.

e14529 Background: Unlike the toxicity, none of the critical prediction markers of CPT-11 efficacy has been validated to date. With a hypothesis that expression analysis of a set of the key drug sensitivity genes could allow us to predict the therapeutic response, we identified potent marker genes for CPT-11 in in vitro, conducted this prospective study attempting to develop a prediction formula of efficacy using the expression data (2006 ASCO, 2006 ESMO), and demonstrated the latest prediction formula of the best tumor response (BTR), time to treatment failure (TTP), and the overall survival after CPT-11 chemotherapy (OS). Methods: Seven genes identified as possible marker genes for CPT-11 (SN-38)- AMD1, CTSC, EIF1AX, FLJ13089 , DDX54, PTPN2, and TBX3-, and 5 other possible marker genes (ABCG2, CYP3A4, MGMT, POR, and TOP2A) that had already been known as drug sensitivity determinants and selected by our in vitro screening process, were studied. CPT-11 was intravenously administered on Days 1, 8, and 15, every 4 weeks in chemo-naive patients with stage IV colorectal cancer after palliative operation. Tumor samples were collected at surgery and tumor response was evaluated by RECIST. Results: All of the 44 enrolled patients were assessable for BTR (% of initial tumor size), TTP (day), and OS (day) in the clinical study, and we successfully developed the best linear model for each, which converted the quantified expression data of the 7 selected genes into objective BTR, TTP, and OS. We used 20, 16, and 15 tumor specimens and constructed potent prediction formulae for BTR (r=0.9420), TTP (r=0.7103), and OS (r=0.8406), respectively. Utility-confirmation analyses using another 16, 10, 13 clinical samples appeared to show that the formulae could predict BTR (r=0.6491, p=0.007) and OS (r=0.7947, p=0.011). We also fixed the best linear models using 5 other known marker genes, but they had less advantage in prediction. Conclusions: Despite limited data, our developed formulae using the 7 novel genes would provide advantages in prediction of individual response to CPT-11. Based on the positive results of this study, we have initiated a large scale validation study of the formula. [Table: see text]