[Subcutaneous continuous injection of octreotide decreased the tumor marker levels and induced cystic necrosis of the tumors in a case of pancreatic neuroendocrine tumor with multiple hepatic metastases].

For symptom alleviation, subcutaneous continuous injection of octreotide was administered to a patient with pancreatic neuroendocrine tumor (NET) accompanied by multiple hepatic metastases and ascites. The level of the tumor marker neuron-specific enolase decreased to the normal range and cystic necrosis of the tumors was confirmed. There have been some reports on the antineoplastic effects of octreotide on pancreatic NET; therefore, octreotide appears to be a valid option as a therapeutic agent in patients with highly advanced pancreatic NET, in whom administration of molecular targeted or anticancer agents is difficult because of a poor general status.

Production of a recombinant mouse monoclonal antibody in transgenic silkworm cocoons.

In the present study, we describe the production of transgenic silkworms expressing a recombinant mouse mAb in their cocoons. Two transgenic lines, L- and H-, were generated that carried cDNAs encoding the L- and H-chains of a mouse IgG mAb, respectively, under the control of the enhancer-linked sericin-1 promoter. Cocoon protein analysis indicated that the IgG L- or H-chain was secreted into the cocoons of each line. We also produced a transgenic line designated L/H, which carried both cDNAs, by crossing the L- and H-lines. This line efficiently produced the recombinant mAb as a fully assembled H(2)L(2) tetramer in its cocoons, with negligible L- or H-chain monomer and H-chain dimer production. Thus, the H(2)L(2) tetramer was synthesized in, and secreted from, the middle silk gland cells. Crossing of the L/H-line with a transgenic line expressing a baculovirus-derived trans-activator produced a 2.4-fold increase in mAb expression. The recombinant mAb was extracted from the cocoons with a buffer containing 3 m urea and purified by protein G affinity column chromatography. The antigen-binding affinity of the purified recombinant mAb was identical to that of the native mAb produced by a hybridoma. Analysis of the structure of the N-glycans attached to the recombinant mAb revealed that the mAb contained high mannose-, hybrid- and complex-type N-glycans. By contrast, insect-specific paucimannose-type glycans were not detected. Fucose residues alpha-1,3- and alpha-1,6-linked to the core N-acetylglucosamine residue, both of which are found in insect N-glycans, were not observed in the N-glycans of the mAb.

Serum anti-myomegalin antibodies in patients with esophageal squamous cell carcinoma.

In order to identify new serum markers of esophageal squamous cell carcinoma (SCC), we performed serological identification of antigens by recombinant cDNA expression cloning (SEREX). E. coli was transformed with a lambdaZAPII phage cDNA library prepared from mRNA of an esophageal cancer cell line (T.Tn), and IPTG-induced cDNA products were screened for interaction with antibodies in allogeneic sera of patients with esophageal SCC. We identified myomegalin (MMGL, phosphodiesterase 4D interacting protein/PDE4DIP) as a new SEREX antigen for esophageal SCC. Western blot analysis revealed that serum anti-myomegalin antibodies (s-MMGL-Abs) were present in 43 (47%) of 91 patients, but in only one (2.2%) of 45 healthy controls. Of the 21 patients with stage I disease, 8 (38%) were sero-positive. The positive rate of s-MMGL-Abs was greater than those of other conventional tumor markers. Reverse transcription-PCR analysis suggested that alternative splicing from myomegalin variant 1 to variant 5 may explain, in part, the development of s-MMGL-Abs. Although the presence of s-MMGL-Abs was not related to any clinicopathological features of the patients, multivariate analysis indicated that the presence of s-MMGL-Abs was significantly associated with a favorable prognosis. Consequently, s-MMGL-Abs may be a useful tumor marker to diagnose and establish a prognosis in patients with esophageal SCC.

Expression pattern of the scaffold protein IQGAP1 in lung cancer.

IQGAP1 is a scaffold protein whose function relates to signal transduction, cell adhesion, local invasion, and distant metastasis of cancer cells. We examined the expression patterns of this protein and clinicopathologic features of lung cancer, and the antibody against IQGAP1 was used for immunohistochemical analysis. Of the 70 surgical specimens examined, there were 40 adenocarcinomas, 19 squamous cell carcinomas, 5 large cell carcinomas, 3 small cell carcinomas, 2 carcinoid tumors, and 1 mucoepidermoid carcinoma. The localization of IQGAP1 was classified into three types: 1) cytoplasmic, 2) membranous, and 3) reduced expression. In adenocarcinoma, the 3 types were observed equally, and differentiation grade was related to the expression pattern. The cytoplasmic type was common in well-differentiated adenocarcinomas, and membranous or reduced expression was frequently seen in moderately- or poorly-differentiated adenocarcinomas. In squamous cell carcinoma, the membranous type was most common. Although the staining pattern of IQGAP1 did not correlate with the positivity of regional lymph nodes, survival in those patients with a cytoplasmic type was significantly better than others with adenocarcinoma (p=0.0144). Expression typing of IQGAP1 in lung cancer was associated with histologic type and can be used to predict survival in patients with adenocarcinoma of the lung.

[Anti-allergic drugs inhibit the proliferation of human Tenon's capsule fibroblast and maintain the experimental filtering blebs on rabbit eyes].

PURPOSE: To examine whether tranilast and ketotifen fumarate inhibit the growth of human Tenon's capsule fibroblasts and maintain experimental filtering blebs on rabbit eyes. METHODS: Human Tenon's capsule fibroblasts were grown in Dulbecco's modified Eagle's medium with 10% fetal calf serum and growth was measured with 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and direct counting of cell number. Production of collagen and transforming growth factor-beta 1 (TGF-beta 1) was measured with corresponding enzyme-linked immunosorbent assay (ELISA). In experimental filtering surgery performed on rabbit eyes, the effects of the topical drugs on intraocular pressure and on maintenance of the filtering blebs were observed. RESULTS: Both tranilast and ketotifen inhibited the growth of the fibroblasts and half-inhibitory concentrations were 200 microM and 70 microM, respectively. Low concentration (10 microM) of tranilast and ketotifen decreased the synthesis of collagen but neither drug had any obvious effect on TGF-beta 1 production. Both drugs prolonged the life of the experimental filtering bleb significantly [12.5 +/- 3.2 (mean +/- standard deviation) days, 13.9 +/- 3.4 days, respectively; control, 10.5 +/- 2.4 days]. CONCLUSION: Tranilast and ketotifen inhibited the growth of human Tenon's capsule proliferation and are capable of maintaining experimental filtering blebs in rabbit eyes.