[A cytofluorimetric analysis of the DNA content and S phase in intraepithelial neoplasia of the cervix uteri]. / Analisi citofluorimetrica del contenuto in DNA e fase S nelle neoplasie intraepiteliali della cervice uterina.

The natural history of cervical intraepithelial neoplasia (CIN) evidenced in such pathologies a different biological behaviour due to the presence of similar morphological atypia with different potential development. To biologically characterize CIN lesions we valued by flow cytometry, the DNA content and the proliferative activity of 53 biopsies obtained by colposcopy. Aneuploid histograms were present in none of the histologically negative lesions, in 14% of the CIN I, in none CIN II, and in 40% of the CIN III. The mean value of S-phase was 2.7% in non dysplastic lesions, 5% in the CIN I, 2.5% in the CIN II and 6.1% in the CIN III. In this study the findings of aneuploid cells and the value of proliferative activities seems to be not correlated with the histological features. The clinical and instrumental follow up of the considered patients could establish the eventual prognostic significance of cytofluorimetric parameters in CIN lesions.

Biologic characterization of pleural metastases from lung adenocarcinoma: description of the new DV90 cell line.

AIMS AND BACKGROUND: The characterization of pleural metastases from lung adenocarcinoma is often limited to single biologic features. METHODS: The present paper describes the cellular kinetic parameters, as well as immunocytochemical, ultrastructural and genetic characteristics of the new DV90 cell line, established from the pleural effusion of a stage IV lung adenocarcinoma. RESULTS: The cell line has a diploid DNA content, a doubling time of 24 h and 7% cloning efficiency, it is tumorigenic in nude mice. Ultrastructural investigation revealed the typical features of lung adenocarcinoma; the diagnosis was confirmed by its immunohistochemical reactivity with a panel of monoclonal antibodies specifically capable of identifying adenocarcinoma cells. Genetic analysis revealed a 46 X, -Y, +8, der (6)t(6?)(q27;?) karyotype and hyperexpression of the protein codified by genes Her2/Neu and p53. CONCLUSION: The importance of multidisciplinary biologic characterization in identifying the origin and biological behavior of pleural metastases deriving from lung adenocarcinoma is discussed.

Synergism between gamma interferon and doxorubicin in a human MDR colon adenocarcinoma cell line.

Recent interest in cancer therapy derives from the ability of interferons to synergistically increase the activity of chemotherapeutic agents. To understand the biological basis of this synergism we evaluated the effects of human recombinant IFN-gamma on the expression of the mdr1 gene and on the cellular growth of a human colon adenocarcinoma cell line (LoVo) and its MDR subline (LoVo/Dx) after coincubation with doxorubicin. Treatment with IFN-gamma showed unchanged levels of MDR1-glycoprotein, no perturbation on cell cycle distribution and a significant reduction of colony formation in both lines (P < 0.05) starting from 100 U/ml. A synergistic effect was observed in the LoVo/Dx cell line when doxorubicin was added after exposure to 0.1-10 U/ml of IFN-gamma. Our data indicate that the effects of IFN-gamma, independent from action on cell proliferation and from modulation of p-glycoprotein expression, are a cause of the synergistic activity between this lymphokine and conventional chemotherapeutic agents such as doxorubicin.

GM-CSF production in human adenocarcinoma cell lines.

We describe the production of human granulocyte-macrophage colony-stimulating factor (hGM-CSF), by cell lines established from patients with different stages of breast, lung and colon adenocarcinoma. GM-CSF expression has been identified by immunocytochemistry determination, quantified on conditioned medium with specific ELISA procedure and evaluated by means of proliferation and differentiation of normal human monocytic and granulocytic progenitors. The growth of cell lines after incubation with exogenous GM-CSF and antibody-antiGM-CSF was not modified. To better understand the patho-physiologic role of hGM-CSF in vivo we also estimated its serum levels at diagnosis in 75 patients with breast lung and colon adenocarcinoma and in 69 healthy person. Only two patients showed detectable GM-CSF levels. The lack of growth modulation observed in vitro with exogenous GM-CSF and antibody anti-GM-CSF suggests a non autocrine secretion by adenocarcinoma cells. The serum investigation evidences that the leukocytosis observed in adenocarcinoma patients is unrelated to a GM-CSF constitutive tumor production in vivo.