Postoperative adjuvant chemotherapy with cisplatin and fluorouracil is better able to prevent relapse in patients with esophageal cancer than surgery alone.

Inorder to determine the operative indications of three-field lymph node dissection of esophageal cancer, attempts were made to collect data concerning procedures performed between 1983 and 1989 in major institutions in Japan, and the results from institutions performing three-field or two-field lymph node dissection were compared. The treatment results of three-field lymph node dissection were better than those after two-field dissection, except for early or advanced cancer. The survival rate improved by the three-field as compared with the two-field lymph node dissection; however,, since surgery was invasive, some complications such as recurrent nerve paralysis were frequent. The results show that the indication of three-field lymph node dissection has to be carefully determined for each patient.

CTLA-4 is a costimulation receptor that binds to the same ligands, CD80 and CD86, as CD28 with high affinity and is transiently expressed on the cell surface of activated T cells. CTLA-4 delivers an inhibitory signal through association of a phosphotyrosine-containing motif in the cytoplasmic domain with Syp tyrosine phosphatase. We now demonstrate that CTLA-4 interacts with the mu2 subunit of the plasma membrane-associated adaptor complex, AP-2, through the same motif involved in the interaction with Syp, except that the interaction with mu2 requires unphosphorylated tyrosine. The interaction with mu2 likely induces rapid internalization of CTLA-4 from the cell surface. Our results suggest that the phosphorylation state of a single tyrosine residue determines whether CTLA-4 delivers a negative signal or is internalized.

Ras gene is one of the oncogenes most commonly detected in human cancers and consists of three families (H-ras, K-ras, N-ras) that are converted to active oncogenes by point mutations occurring in codon 12, 13, or 61. The authors analyzed mutations of these codons in 12 extrahepatic bile duct carcinomas, nine gallbladder carcinomas, and 20 pancreatic tumors (18 pancreatic adenocarcinomas and two islet cell tumors) by a method to directly sequence nucleotides, using polymerase chain reaction and a direct sequencing method. Point mutations at K-ras codon 12 were found in all of 18 pancreatic adenocarcinomas and in one bile duct carcinoma, but there were no mutations in the remaining 11 bile duct carcinomas, in all of 9 gallbladder carcinomas, or in two islet cell tumors. A very high incidence of ras gene mutations may be used clinically for the diagnosis of debatable cases of pancreatic adenocarcinoma.

Postoperative adjuvant chemotherapy with cisplatin and vindesine has no additive effect on survival in patients with esophageal cancer compared with surgery alone.

Daily continuous infusion of cisplatin was not associated with higher response or lower toxicity than those seen with the high-dose bolus or multibolus treatment regimens. We conclude that this regimen in this setting is not worthy of further phase III trials. JEOG is now evaluating other drug combination regimens.

The mammalian mel‐18/bmi‐1 gene products share an amino acid sequence and a secondary structure, including a RING‐finger motif, with the Drosophila Polycomb group (PcG) gene products Psc and Su(z)2, implying that they represent a gene family with related functions. As Drosophila PcG gene products are thought to function as transcriptional repressors by modifying chromatin structure, Mel‐18/Bmi‐1 might be expected to have similar activities. Here we have analyzed the function of mel‐18 and found that Mel‐18 acts as a transcriptional repressor via its target DNA sequence, 5′‐GACTNGACT‐3′. Interestingly, this binding sequence is found within regulatory or non‐coding regions of various genes, including the c‐myc, bcl‐2 and Hox genes, suggesting diverse functions of mel‐18 as the mammalian homolog of the PcG gene. We also demonstrate that mel‐18 has tumor suppressor activity, in contrast to bmi‐1, which has been defined as a proto‐oncogene.

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