[Bi-weekly docetaxel and doxifluridine combination therapy in pretreated patients with unresectable and/or advanced gastric cancer].

We report an investigation of the therapeutic efficacy and safety of combination chemotherapy with docetaxel (DOC) and doxifluridine (5'-DFUR) administered as second-line or third-line chemotherapy in 23 cases of unresectable and/or advanced gastric cancer. Treatment consisted of intravenous DOC (40mg/m/2) on day 1 and 15, and oral 5'-DFUR (600mg/body) on days 1 to 28 every 4 weeks. The response rate for its antitumor efficacy was 17.4 %, with partial response in 4 cases, no change in 6 cases, progressive disease in 12 cases, and one case not evaluable. By site, the response rate was 11. 8% for primary tumors (2/17), 33.3% for lymph nodes (3/9) , and 26.9% for liver metastasis (1/7). Median time to treatment failure was 2.6 months, median overall survival was 4.6 months. The one-year survival rate was 26.1 %, and the two-year survival rate was 13.0%. The most common grade 3 to 4 toxicities were neutropenia( 4.3%), fatigue (8.7%), stomatitis (8.7%), anorexia(4.3% ), and rash (4.3%). Our data suggest that the combination of docetaxel and 5'-DFUR has a promising therapeutic index in patients with unresectable advanced gastric cancer as second-line or third-line chemotherapy.

Inhibition of the 53BP2S-mediated apoptosis by nuclear factor kappaB and Bcl-2 family proteins.

The p53 binding protein 2 (53BP2) has been identified independently as the interacting protein to p53, Bcl-2, and p65 subunit of nuclear factor kappaB (NF-kappaB). It was demonstrated that over-expression of 53BP2 (renamed as 53BP2S) induces apoptotic cell death. In this study we explored the effect of NF-kappaB activation elicited by a physiological NF-kappaB inducer, interleukin-1beta (IL-1beta), and anti-apoptotic Bcl-2 family proteins on the 53BP2S-mediated apoptosis. We found that both NF-kappaB activation and Bcl-2 family proteins could prevent the 53BP2S-mediated depression of mitochondrial transmembrane potential, activation of caspase-9, cleavage of poly ADP ribose polymerase (PARP), and cell death. These observations suggested that 53BP2S/Bbp and its directly or indirectly interacting proteins might play crucial roles in the regulation of apoptosis and contribute to carcinogenesis. It is also suggested that 53BP2S/Bbp induces apoptosis through the mitochondrial death pathway presumably by counteracting the actions of anti-apoptotic Bcl-2 family proteins. The regulatory network of the 53BP2S-mediated apoptosis cascade including its interacting proteins is discussed.

53BP2 induces apoptosis through the mitochondrial death pathway.

The p53 binding protein 2 (53BP2) has been identified as the interacting protein to p53, Bcl-2, and p65 subunit of nuclear factor kappaB (NF-kappaB). The TP53BP2 gene encodes two splicing variants, 53BP2S and 53BP2L, previously known as apoptosis stimulating protein 2 of p53 (ASPP2). We found that these 53BP2 proteins are located predominantly in the cytoplasm and induce apoptosis as demonstrated by cleavage of poly ADP ribose polymerase (PARP) and annexin V staining. Furthermore, we demonstrate that 53BP2 is located in the mitochondria and induces apoptosis associated with depression of the mitochondrial trans-membrane potential (DeltaPsim) and activation of caspase-9. From these findings we conclude that 53BP2 induces apoptosis through the mitochondrial death pathway.

Efficacy of plastic tube stents without side holes for middle and lower biliary strictures.

BACKGROUND: Although biliary expandable metallic stents (EMS) improve patency, they are unsuitable for primary biliary stenting. Although plastic tube stents without side holes (PWOS) are also reported to prolong patency, their efficacy remains controversial. GOALS: To evaluate clinical utility and relative advantages, we reviewed clinical results of three types of stents: plastic tube stents with side holes (PS), PWOS, and EMS. STUDY: The 130 patients comprised 56 with pancreatic cancers, 26 with gallbladder cancers, 21 with bile duct cancers, and 27 with other malignant diseases. Plastic tube stents with side holes (10 French [Fr]), PWOS (10 Fr), and EMS (30 Fr) were inserted in 64, 28, and 38 cases, respectively. RESULTS: Overall cumulative stent patency rates for EMS and PWOS groups were significantly higher than that of PS. This was also the case with middle and lower biliary tract strictures and with pancreas cancers. In Japan, medical costs with endoscopic retrograde cholangiopancreatography ($631.00) divided by the mean patent period with PS, PWOS, and EMS were $8.80/d, $4.60/d, and $20.40/d, respectively. CONCLUSION: We recommend PWOS for primary biliary stenting of middle and lower biliary strictures, especially those caused by pancreatic cancer, based on its lower price and sufficient patency without replacement after diagnosis of inoperability.