The EGF stimulation system for growth regulation is implicated in normal and neoplastic cell proliferation. The role of EGF, the EGF receptor, and c‐erbB‐2 in human gastric cancer is reviewed on the basis of several reports, which have been mainly oriented toward their clinical significance. EGF has been shown immunohistochemically to be present in 26% of gastric cancers (n = 395). The presence of EGF in gastric cancer is correlated with the degree of gastric wall invasion and lymph node metastasis. The 5‐year survival of patients with EGF‐positive tumors is worse than that of patients with EGF‐negative tumors. The presence of EGF in human gastric cancer may therefore represent a higher malignant potential. Fifteen percent of gastric cancers (n = 352) were also shown to be positive for both EGF and the EGF receptor immunohistochemically, and the simultaneous occurrence of EGF and the EGF receptor suggests that these tumors grow in an autocrine fashion. Tumors exhibiting EGF and the EGF receptor simultaneously show a greater degree of local invasion and lymph node metastasis. Increased expression of EGF receptor protein in gastric cancer appears to be related to biologic aggressiveness, although gene amplification has occurred only to a small extent. Twelve percent of gastric cancers (n = 486) were found to be positive for c‐erbB‐2. This type of tumor has a frequent metastasis, and patients with c‐erbB‐2‐positive cancer have a poorer prognosis than those with c‐erbB‐2‐negative tumors. Selective blockade of the EGF receptor and c‐erbB‐2 from their ligands with monoclonal antibodies (MoAbs) inhibits the growth of human gastric cancer xenografts. These MoAbs may therefore be effective antitumor agents against gastric cancer showing overexpression of EGF receptors or c‐erbB‐2. Cancer 1995;75:1418‐25.
AKlRA TOKUNAGA, MD,* KEIGO NISHI, MD,' NORIO MATSUKURA, MD,' NORITAKE TANAKA, MD,' MASAHIKO ONDA, MD,',t AKlRO SHIROTA, MD,$ GORO ASANO, MD.t.9 AND KAZUO HAYASHI, PHD)/ Cancerous tissue from 86 patients with primary gastric cancer were examined for the presence of receptors for estrogen (ER) and progesterone (PgR). ER and PgR were present in 8 (15.4%) and 5 (9.6%), respectively, of 52 male patients, 9 (26.6%) and 7 (20.6%), respectively, of 34 female patients, a total of 17 (19.8%) and 12 (14.0%), respectively. One male patient (1.9%) and 4 female patients (11.8%) had both ER and PgR, and 40 male (76.9%) and 22 female patients (64.7%) showed no ER or PgR. The binding activity ranged from 6 to 200 fmol/mg protein for estradiol and from 5 to 58 fmol/mg protein for progesterone. ER-and/or PgR-positive cases were characterized grossly as Borrmann type 4, and microscopically as diffuse type with scirrhous growth pattern. The presence of ER and/or PgR in some gastric cancers indicates the possibility that sex hormonal factors are involved in these tumors.
A metal-free deoxygenation and reductive disilylation of nitroarenes was achieved using N,N'-bis(trimethylsilyl)-4,4'-bipyridinylidene (1) under mild and neutral reaction conditions, and a broad functional group tolerance was possible in this reaction. Mono-deoxygenation, giving a synthetically valuable N,O-bis(trimethylsilyl)phenylhydroxylamine (7 a) as a readily available and safe phenylnitrene source from nitrobenzene, and double-deoxygenation, giving N,N-bis(trimethylsilyl)anilines 8, were easily controlled by varying the amounts of 1 and reaction temperature as well as adding dibenzothiophene (DBTP). Reaction of 2-arylnitrobenzenes with 1 resulted in the formation of the corresponding carbazoles 14 via in situ-generated phenylnitrene species derived by thermolysis of N,O-bis(trimethylsilyl)phenylhydroxylamines 7, followed by their subsequent intramolecular C-H insertion. In addition, the intramolecular N-N coupling reaction proceeded in the reduction of 2,2'-dinitrobiphenyl derivatives by 1, giving the corresponding benzo[c]cinnolines.
A metathesis reaction of a W[triple bond, length as m-dash]W bond and an N[double bond, length as m-dash]N bond was observed by reacting a W-W triply-bonded W(iii)2 complex, (tBuO)3W[triple bond, length as m-dash]W(OtBu)3 (1), with benzo[c]cinnoline derivatives to form biphenyl-linked dinuclear (imido)tungsten complexes 2-4. When azobenzene was used as the substrate, a trans to cis isomerization induced by blue-LED light was essential prior to the metathesis cleavage of the N[double bond, length as m-dash]N bond by the W[triple bond, length as m-dash]W bond of (Me2N)2(TfO)W[triple bond, length as m-dash]W(OTf)(NMe2)2 (6), affording the corresponding imido-bridged dinuclear tungsten complexes 7-9.
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