Two cases of bile duct carcinoma patients who underwent the photodynamic therapy using talaporfin sodium (Laserphyrin®).

The efficacy of adjuvant photodynamic therapy (PDT) using the new photosensitizer, talaporfin sodium (TPS) has been clinically examined in some patients with bile duct carcinoma (BDC). Based on our previous cohorts, a prospective clinical trial was attempted; however, only two cases were ultimately enrolled in 27 months. A 664-nm semiconductor laser (100 J/cm2) was applied through an endoscope to the tumor lesion within 6 h of an intravenous injection of 40 mg/m2 TPS according to the protocol for lung cancer. Case 1 was an 82-y.o. female patient with BDC at the left hepatic duct with biliary obstruction, percutaneous transhepatic biliary drainage (PTBD) was achieved, and the patient did not consent to surgery. She was followed up for 15 months to search for non-surgical treatments and eventually received PDT. Although mild photosensitivity occurred, she was discharged without severe adverse events. Biliary stenosis markedly extended and a PTBD tube was scheduled at 1 month. However, cancer immediately metastasized to the liver and she died 155 days after PDT. Case 2 was a 70-y.o. female with perihilar BDC and multiple biliary stenoses. Multiple biliary stenting was considered to be difficult. She received PDT and no adverse events were observed. Biliary stenoses markedly improved and multiple stenting was successfully performed. On day 132, she died of cancer progression. These two cases demonstrated the safety and efficacy of biliary malignant stenosis soon after PDT; however, long-term survival and a sufficient quality of life were not achieved. The combination of the PDT protocol and system chemotherapy or brachytherapy needs to be examined in clinical trials for advanced stage BDC.

Identification and characterization of a novel human type II diacylglycerol kinase, DGK kappa.

Diacylglycerol kinase (DGK) plays an important role in signal transduction through modulating the balance between two signaling lipids, diacylglycerol and phosphatidic acid. Here we identified a tenth member of the DGK family designated DGK kappa. The kappa-isozyme (1271 amino acids, calculated molecular mass, 142 kDa) contains a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region as have been found commonly for the type II isozymes previously cloned (DGKdelta and DGKeta). The new DGK isozyme has additionally 33 tandem repeats of Glu-Pro-Ala-Pro at the N terminus. Reverse transcriptase-PCR showed that the DGK kappa mRNA is most abundant in the testis, and to a lesser extent in the placenta. DGK kappa, when expressed in HEK293 cells, was persistently localized at the plasma membrane even in the absence of cell stimuli. Deletion analysis revealed that the short C-terminal sequence (amino acid residues 1199-1268) is necessary and sufficient for the plasma membrane localization. Interestingly, DGK kappa, but not other type II DGKs, was specifically tyrosine-phosphorylated at Tyr78 through the Src family kinase pathway in H2O2-treated cells. Moreover, H2O2 selectively inhibited DGK kappa activity in a Src family kinase-independent manner, suggesting that the isozyme changes the balance of signaling lipids in the plasma membrane in response to oxidative stress. The expression patterns, subcellular distribution, and regulatory mechanisms of DGK kappa are distinct from those of DGKdelta and DGKeta despite high structural similarity, suggesting unique functions of the individual type II isozymes.