No abstract

We studied whether a novel vasoconstrictor peptide, endothelin-i (ET-I), is synthesized by and released from human carcinoma cell lines, and whether ET-1 stimulates proliferation of these tumor cells. ET-1-like immunoreactivity was released from both HeLa and HEp-2 cells as a function of time. Reverse-phase HPLC of the conditioned media from HeLa cells revealed a major peak coeluting with standard ET-1. Northern blot analysis demonstrated the expression of mRNA for ET-1 precursor in both tumor cell lines. Both cell lines contained a single class of specific binding sites for ET-1. ET-1 dose-dependently induced increases in cytosolic free Ca2" concentration in fura-2-loaded tumor cells, whose effect was completely abolished by chelating extracellular Ca2" or by Ca2"-channel blocker. ET-1 stimulated proliferation of the quiescent cell lines in a dose-dependent manner, whose effect was inhibited by Ca2-channel blocker. Polyclonal antibody for ET-1 inhibited proliferation of these cell lines, whereas nonimmune serum had no effect. These results demonstrate that ET-1 is synthesized by and released from human epithelial carcinoma cell lines, and that exogenous and endogenous ET-1 stimulates proliferation of the cells possibly through Ca2" influx, suggesting its role as an autocrine/paracrine growth factor for certain tumor cells. (J.

Nodular hepatic lesions detected in 123 patients with chronic liver diseases were subjected to ultrasonically guided needle biopsy. Of these, 94 cases were diagnosed as hepatocellular carcinoma of a moderately or poorly differentiated type with classical histologic features of hepatocellular carcinoma. In 14 cases in whom hepatocytes had minimal atypical changes and were mostly of normotrabecular arrangement (one to two cells thick), a diagnosis of well-differentiated hepatocellular carcinoma was made on the basis of the following three histologic criteria: nuclear crowding, increased cytoplasmic basophilia and microacinar formation. The nodules which showed two or more of these findings were diagnosed as well-differentiated HCC. The diagnoses of these 14 cases were subsequently confirmed by clinical course, histology in the resected specimen and/or autopsy findings. The nodules that presented similar but equivocal changes were arbitrarily categorized as borderline lesions (five cases). The nodules showing the findings almost identical with those of pseudolobules were regarded as benign, large regenerative nodules (nine cases). The remaining one case had a hemangioma. Thus, these three histologic criteria proved to be useful in the biopsy diagnosis of nodular hepatic lesions, with certain limitations. Additionally, the majority of large regenerative nodules, borderline lesions and well-differentiated HCCs were found to be smaller than 2 cm.

Optimized geometries and energies in the ground (S0) and excited states of nitrobenzene were calculated using the CAS-SCF method. The optimized geometries in the S1, S2, T1, T2, and T3 states are very different from that in the S0 state. Most significantly, the nitro group is largely bent out of the phenyl plane in the excited states. The potential curves along the nitro rotation coordinate around the C−N bond and the out-of-plane bending mode of the nitro group in the S0, S1, T1, and T2 states were calculated in relation to the excited states dynamics. It is found that the potential curves along the bending mode in the excited states are very flat compared with that in the S0 state. The mechanisms for the fast relaxation from the S1 and T1 states are discussed based on the ab initio results.

S. OHMOMO, S. MURATA, N. KATAYAMA, S. NITISINPRASART, M. KOBAYASHI, T. NAKAJIMA, M. YAJIMA and K. NAKANISHI.2000. Bacteriocin‐like activity (BLA) was screened in 690 strains of lactic acid bacteria isolated from plant materials such as silages and fermented vegetables. Among them, a strain identified as Enterococcus faecium NIAI 157 showed a clear BLA against the indicator strain, Ent. faecium IFO 13712. The proteinaceous nature and antimicrobial activity against closely related species strongly indicated that this BLA was a bacteriocin and was designated enterocin ON‐157. The bacteriocin activity of this strain was extracellularly produced in the logarithmic growth phase in MRS broth and purified by ultrafiltration, ammonium sulphate precipitation and cation‐exchange chromatography. Purified enterocin ON‐157 had a molecular weight of approximately 2500 Da in SDS‐PAGE analysis and was easily inhibited by treatment with α‐amylase and proteolytic enzymes. Enterocin ON‐157 had a bactericidal mode of action and inhibited the growth of the enterococci, Lactobacillus sake and Listeria monocytogenes. Enterococcus faecium NIAI 157 harboured two plasmids, 49·0 kb and 43·7 kb, and a variant missing a larger plasmid by curing with novobiocin lost the bactriocin activity.

Eleven cases of cholangiocarcinoma containing a component of squamous cell carcinoma (CC‐SCC) were reviewed clinicopathologically in comparison with 82 cases of common cholangiocarcinoma presenting as a pure form of adenocarcinoma (CC‐AC). The former type was prone to develop in a rather advanced stage of the disease, as indicated by short survival time, large tumor size, aggressive modes of intrahepatic spreading, and frequent metastasis. Histologically, the area of squamous cell carcinoma ranged from focal to overwhelming. The occurrence of the squamous element could be interpreted as the result of the metaplastic transformation of adenocarcinoma cells because of the intimate coexistence of the two types in the primary and metastatic lesions. It also was suggested that anaplastic carcinoma cells could sometimes differentiate into squamous cell carcinoma. In no instances was there any squamous metaplasia of the bile ducts demonstrated; therefore, there was no supporting evidence for the possibility of squamous metaplasia of the bile duct epithelium and subsequent malignant transformation.

Background. Although there have been a few reports dealing with the sarcomatous changes of intrahepatic cholangiocarcinoma, its clinicopathologic features as well as immunohistochemical nature remain obscure. Methods. Among 155 cases of intrahepatic cholangiocarcinoma, 7 cases of sarcomatous cholangiocarcinoma were chosen. Immunohistochemical studies using the avidin‐biotin‐peroxidase complex method were performed on these cases. Results. The tumor showed both mucin‐producing adenocarcinoma areas and sarcomatous areas, the latter being predominant in three cases and focal in the other four. All the sarcomatous areas consisted of atypical spindle cells arranged in sheets or bundles. Pleomorphic giant cells were observed in some sarcomatous components in five cases. Immunohistochemical staining for keratin and epithelial membrane antigen revealed apparent positivity in the sarcomatous components of five cases. The patients with these tumors showed aggressive intrahepatic spreading and widespread metastasis of the sarcomatous cells, and demonstrated poorer prognosis than those with ordinary cholangiocarcinoma, with one exception, a patient who remained disease‐free for 3 years after surgery. Conclusions. These findings favor the possible epithelial origin of sarcomatous cells. Radical operation would be necessary for patients with this special type of cholangiocarcinoma.

Nine cases of biliary cystadenocarcinoma of the liver were studied, with emphasis on its clinicopathologic features, mucin profiles, and immunohistochemical characteristics. In general, the cystic tumors had protrusions that consisted of well‐differentiated papillary adenocarcinoma cells with or without benign‐appearing epithelial elements. In invading or metastatic foci, the carcinoma cells tended to show distinctive anaplastic changes. Tumor growth was confined to the cystic lesions in five cases (noninvasive type), whereas in four cases it extended to the hepatic parenchyma or neighboring organs (invasive type). There was a considerable difference between the two groups in terms of prognosis. In fact, the patients included in the group with the noninvasive type had no sign of tumor recurrence after an appropriate surgical procedure. With mucin histochemical and immuno‐histochemical approaches, positive reactions with car‐cinoembryonic antigen, tissue polypeptide antigen, carbohydrate 19‐9, and Dupan‐2 and the predominance of sialomucin were observed in most cases of biliary cysta‐denocarcinoma, indicating a similar cellular nature of cholangiocarcinoma. Cancer 1992; 69:2426‐2432.