[Features of surgical treatment of central tracheal and bronchial carcinoid]. / Osobennosti khirurgicheskogo lecheniya tsentral'nogo kartsinoida trakhei i bronkhov.

OBJECTIVE: To analyze features of surgical treatment of central tracheal and bronchial carcinoid. MATERIAL AND METHODS: A retrospective analysis included 115 patients with carcinoid tracheal and bronchial tumors who have been examined and treated from 1974 to the present. The majority of patients (97, 84.3%) had central form of carcinoid of the trachea, bronchi and lungs. Of these, 95 (97.9%) ones underwent surgical treatment. RESULTS: We used pre- and intraoperative diagnostics including bronchotomy. This approach provided organ-sparing surgery with resection and reconstruction of the bronchi and trachea in 71 (74.7%) patients including complete preservation of lung function in 20 (21.1%) cases and lobectomy/segmentectomy with resection and reconstruction of the bronchi in 51 (53.7%) cases. Two patients underwent pneumonectomy with wedge-shaped and marginal resection and reconstruction of tracheal bifurcation. Postoperative complications developed in 4 (4.2%) patients, and 2 (2.1%) ones died. Overall 5-year survival after radical surgeries was 89.2% (100% in typical carcinoid and 78.0% in atypical carcinoid).

Ah-receptor-independent stimulation of hepatoma 27 culture cell proliferation by polycyclic aromatic hydrocarbons.

The proliferative effect of some compounds that are aryl hydrocarbon (Ah) receptor ligands was studied on hepatoma 27 cells with absent expression of Ah receptor. Compounds of the polycyclic aromatic hydrocarbon (PAH) class benzo/a/pyrene, 3-methylcholanthrene, 7,12-dimethylbenz/a/anthracene, and benzo/e/pyrene as well as ß-naphthoflavone (ß-NF) and chlorinated hydrocarbon Aroclor 1254 were studied. It was found that carcinogenic PAH and ß-NF stimulate cell proliferation both under conditions of standard serum content and in a medium with low serum content. More efficient stimulation of proliferation was observed in the case of low serum content. Aroclor 1254 and benzo/e/pyrene did not stimulate cell proliferation. Stimulation of proliferation was accompanied by activation of the ERK1/2-dependent MAP-kinase cascade. Benzo/a/pyrene caused a decrease in the number of cells in G1 phase of the cell cycle and increase in number of cells in G2/M phases under conditions of cell growth in media with low serum content. Carcinogenic PAH and ß-NF activated transcription factor AP-1, and in this case activation was more pronounced in cells grown in medium with low serum content. A possible mechanism of activation of proliferation by an Ah receptor-independent pathway is discussed.

[Ah receptor-independent inhibition of gap junction intercellular communications in hepatoma cell culture 27 by polycyclic aromatic hydrocarbons].

One of the systems that regulate tissue homeostatis is gap junction intercellular communications (GJIC). Inhibition of GJIC is widely used in experiments as a characteristic of tumor promotion. It is accepted that the down-regulation of GJIC is tightly related with the tumor-promoting properties of carcinogens. In this study, the effect of some carcinogenic polycyclic aromatic hydrocarbons on GJIC in cell cultures of hepatoma 27 lacking cytochrome P450 and Ah receptor was investigated. It was shown that inter 6 compounds studied only benzo/a/pyren and 3-methylcholanthrene were able to inhibit GJIC. We have concluded that an unknown factor is present in hepatoma cells and its interaction with some polycyclic aromatic hydrocarbons results in GJIC inhibition. The investigation of mutual effect of benzo/a/pyrene and non carcinogenic benzo/e/pyrene with similar structure has shown that GJIC inhibition by benzo/a/pyrene is at least double stepped.

Benzo[a]pyrene-dependent activation of transcription factors NF-kappaB and AP-1 related to tumor promotion in hepatoma cell cultures.

The activation by the carcinogenic polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BP) of transcription factors NF-kappaB and AP-1 in hepatoma 27 and HepG2 cell cultures was studied. In contrast to the hepatoma HepG2 cells, cytochrome P450 isoforms and Ah-receptor are not expressed in the hepatoma 27 cells. The transcription factor NF-kappaB was activated only in the hepatoma 27 cells by BP treatment but not by its noncarcinogenic isomer benzo[e]pyrene (BeP). Conversely to NF-kappaB activation the transcription factor AP-1 was activated in the hepatoma HepG2 cells by cell treatment with BP but not in the hepatoma 27 cells. It is concluded that the NF-kappaB activation is caused by nonmetabolized BP molecule and not related to activation of the Ah-receptor. The transcription factor AP-1 seems to be activated as a result of the interaction of BP with the Ah-receptor. The realization of tumor promotion stage by carcinogenic PAHs treatment in dependence on the cytochrome P450 and Ah-receptor levels in the initiated cells is discussed.