Effect of rapamycin on mouse chronic lymphocytic leukemia and the development of nonhematopoietic malignancies in Emu-TCL1 transgenic mice.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the world. The TCL1 gene, responsible for prolymphocytic T cell leukemia, is also overexpressed in human B cell malignancies and overexpression of the Tcl1 protein occurs frequently in CLL. Aging transgenic mice that overexpress TCL1 under control of the mu immunoglobulin gene enhancer, develop a CD5+ B cell lymphoproliferative disorder mimicking human CLL and implicating TCL1 in the pathogenesis of CLL.

Establishment and characterization of four cell lines derived from human head and neck squamous cell carcinomas for an autologous tumor-fibroblast in vitro model.

To study interactions between tumor cells and stromal elements, we established carcinoma cell lines as well as tumor-derived and skin fibroblast cultures from four patients with squamous cell carcinoma of the head and neck. For the characterization of the tumor cell lines we a) determined population doubling times, b) assessed morphological features by light and electron microscopy, c) investigated the expression of typical markers by immunohistochemistry, including various intermediate filaments and surface antigens, d) compared these findings with expression patterns in the respective original tumor specimens, e) evaluated p53 mutations in tumor specimens and cell lines, f) performed chromosome analysis, g) investigated the tumorigenicity in athymic mice, and h) tested the formation of both tumor and mixed tumor-fibroblast multicellular spheroids. Tumor cell cultures were considered established cell lines when maintained and passaged over a period of two years after primary explantation.

A novel human malignant fibrous histiocytoma cell line of the heart (MFH-H) with secretion of hematopoietic growth factors.

Primary malignant fibrous histiocytoma (MFH) exhibits an extremely adverse prognosis. Investigations into the principles determining the biological aggressiveness of this cardiac tumor would be facilitated by an appropriate in vitro model. Therefore, we report on the first permanent cell line (MFH-H), derived from a human cardiac MFH.

Characterization of two newly established cell lines derived from squamous cell carcinomas of the oesophagus.

This study describes characteristics of two newly established cell lines (OSC-1 and OSC-2), derived from two oesophageal squamous cell carcinomas. Morphologically, OSC-1 cells and OSC-2 cells grew in epithelial cobblestone patterns with cells piling up to 4 cells. Ultrastructurally, both cell lines showed formation of desmosomes; however, tonofilaments were only formed by OSC-2 cells.

Chromophilic renal cell carcinoma: cytomorphological and cytogenetic characterisation of four permanent cell lines.

Chromophilic renal cell carcinoma is a distinct type of human renal cancer, only recently recognised and defined by its characteristic histomorphological aspect and cytogenetic aberrations. We are the first to report on the establishment and cytogenetic characterisation of a panel of four permanent cell lines, i.e.

[Expression of cellular antigen of hypopharyngeal carcinoma in different culture conditions].

Background: The need to improve therapy regimes, determine prognosis, and study biological properties of tumors extracorporally led to development of different experimental systems. In order to approach the in vivo situation, specific properties of the tumors of origin should be retained by the cells in culture over relatively long periods. However, culture conditions may change expression of cellular antigens.

Promoting effects of fibroblasts on growth and progression of head and neck carcinoma cells.

Interaction of stroma and tumor cells within a carcinoma can influence tumor growth and progression. We investigated possible influences of allogeneic and autologous fibroblasts on established squamous cell head and neck carcinoma lines (SCHNCL) and freshly isolated cells from such tumors. Tumor cells were compared in their colony-forming ability, starting from low cell counts, in their ability to form multicellular spheroids (MCS) and in their capacity to form tumors in the subrenal capsule of nu/nu mice.

Exposure of organ cultures from human tracheal epithelium to chemical carcinogens and subsequent long-term co-cultivation with autologous isotopic fibroblasts.

As a continuation of previous experiments introducing an extracorporeal model for transformation of human respiratory epithelium that might be able to mimic a spontaneously occurring malignant tumor, we prepared organ cultures from tracheal specimens and exposed them repeatedly to chemical carcinogens, using benzo(a)pyrene and methylnitronitrosoguanine for 6 weeks. We then tried to select possibly initiated cells by subsequent co-cultivation with autologous isotopic fibroblasts for 2 years. Nontreated controls were maintained from the same specimens and cultured in the same manner.

[Morphologic and immunohistochemical studies of organ cultures of human tracheal biopsies].

Most likely the transformation of epithelial cells to carcinoma cells takes place during the process of differentiation. In order to study in vitro carcinogenesis, an experimental system for organ cultures was developed in which human respiratory epithelial from tracheal biopsies differentiate within six weeks. The mucosal and submucosal layer of small tracheal biopsies was cut into pieces measuring 3 x 3 and 5 x 5 mm2, respectively, and placed on Gelita cubes (Braun-Melsungen, Germany) measuring 10 x 10 x 10 mm3 with the epithelium facing up.

Establishment and characterization of two divergent cell lines derived from a human chromophobe renal cell carcinoma.

The chromophobe renal cell carcinoma is a distinct type of renal cancer presumably derived from the intercalated cell of the collecting duct system and exhibiting a better prognosis than other types of renal cell carcinoma. Chromophobe carcinomas can be separated from other types of renal cell carcinoma by their characteristic cytomorphology, ultrastructural appearance, cytoskeletal architecture, and cytogenetic aberrations. As no permanent cell line of the chromophobe tumor type has previously been described, we are the first to report on the successful establishment and characterization of two divergent permanent cell lines, ie, chrompho-A and chrompho-B, derived from the same chromophobe renal cell carcinoma.

Dual role of fibroblasts in tumor cell growth.

Vast experience with cultivating biopsies from human tumors indicates that in most cases the admixture of fibroblasts has a negative effect on growth of tumor cells. Only rarely is observed help provided by the fibroblasts. It has also long been known that fibroblasts can inhibit by contact themselves and also produce growth factor(s) promoting cell proliferation.

Immunohistochemical examination of 11 cell lines derived from human head and neck squamous cell carcinomas, their recurrences or metastases.

Since in vitro derived tumor cell lines usually correspond to their tumors of origin, a potential biological difference between a primary tumor and its derivative metastases and recurrent tumors should be reflected in established tumor cell lines. The aim of this study was to determine useful cellular markers in permanent tumor cell lines of head and neck squamous cell carcinomas (SCC) and to evaluate a possible relationship between these markers and the origin of selected cell lines. The cell lines, established in the laboratory of T.

[Immunohistochemical studies of advanced laryngeal and hypopharyngeal carcinomas 3 days after administration of monoclonal antibody against epidermal growth factor receptor].

Sixteen consecutive patients with stage III/IV laryngeal or hypopharyngeal cancer received 0, 20, 100 or 400 mg i.v. of the murine anti EGF-R IgG2a mab EMD 55900 three days before laryngectomy and neck dissection.

Inhibition of head and neck tumor cell colony growth by lymphokine activated killer cells.

The antiproliferative effect of lymphokine activated killer (LAK) cells on head and neck tumor cells has not previously been elucidated. We studied the inhibitory effects of recombinant interleukin-2 activated lymphocytes on tumor colony formation in semisolid agar, using head and neck tumor cells prepared from established tumor cell lines (K562, HT29, HLaC78) and xenografted head and neck squamous cell carcinomas on nude mice (XKN, XLL, XFL, XKF). LAK cells demonstrated a significant inhibitory effect on colony formation.

Morphologic analysis of three-dimensional tumors developed in fibrin matrix and agar culture system.

The three-dimensional growth of cultured tumor cell lines (HT29, a colon adenocarcinoma cell line; M21, a melanoma cell line; KB, a nasopharyngeal carcinoma cell line) has been investigated in an agar culture system with a fibrin matrix in vitro. The tumor cells developed to tumors 3 x 3 mm in diameter after 10 days in culture in vitro. This size was large enough to allow histologic examination.

Induction of transformation of human respiratory epithelium in vitro. Preliminary investigation.

Malignancy is the result of multistep transformational changes of normal somatic cells. In the case of respiratory epithelial malignancies this process lasts for several years. Many methods have been explored to mimic this process in an extracorporal model.

In vitro and in vivo organ cultures containing respiratory epithelium.

A combination of two methods, organ culture and transplantation under the kidney capsule of nude mice, can be a suitable tool to study the mechanism of carcinogenesis of the human respiratory epithelium and to detect risks in environmental pollution. We used two tissues containing the respiratory epithelium--rat lung and human vocal cord. Gelita, a porous material used in surgery for haemostasis, produces a good support for the growing organ cultures of both tissues.

[Establishing three dimensional tumors in vitro and the reaction of the lymphokine-activated killer cells (LAK) to the three dimensional tumors].

In this study, we attempted to develop a technique, by which three-dimensional tumors were produced from two cultured head and neck tumor cell lines (Hep2, KB) and a colon adenocarcinoma cell line (HT29) using fibrinogen, thrombin, and double layered agar system. The three-dimensional tumor was large enough to perform the histologic study, which showed no significant histologic difference in comparison with the histologic findings of the xenografted tumor on nude mice. Furthermore, we applied this assay model to evaluate the antitumor effect of lymphokine activated killer (LAK) cells on the three-dimensional tumor produced by the technique.

Effect of lymphokine-activated killer cells on head and neck tumours in nude mouse model.

The present study was designed to investigate the in vivo effect of local application of lymphokine-activated killer (LAK) cells on the growth of tumours implanted under the renal capsule in nude mice, and especially to test whether large granular lymphocytes (LGL), regarded as natural killer (NK) cells, are the main precursor of LAK cells in vivo. Our results showed that the local application of LAK cells inhibited the growth of tumours in the head and neck region. The growth of tumours implanted under the renal capsule was inhibited by local application of 1 x 10(7) recombinant interleukin-2 (rIL-2) activated non-adherent lymphocytes, but the inhibitory effect was almost the same as produced by 3 x 10(6) rIL-2-activated LGL application.

[Initial results of immunotherapy approaches to tumor treatment in the animal model].

The possibilities of using immunocytes in cancer therapy have been increasing during the last few years. Contrary to the promising results gained by in vitro experiments, several clinical trials have shown that, on the one hand, it is difficult to preserve a quantity of cells big enough to inhibit tumours, and they have also shown that, on the other hand, antitumour lymphocytes do not get into the tumour. That is why we concentrated on improving the tumour selectivity of the antitumour lymphocytes.

Use of the subrenal capsule assay to measure antibody-dependent, cell-mediated cytotoxicity against head and neck tumors.

Experience with antibody-dependent, cell-mediated cytotoxicity (ADCC) has shown that antibody can increase the localization and killing capacity of lymphocytes. We tested the possibility of improving the activity of lymphokine-activated killer cells (LAK) on human tumor using the subrenal capsule assay in nude mice. The tumors were first grown in the renal capsule space and the effector cells injected later.

The anti-tumor effect of in vitro tumor-stimulated autologous peripheral blood lymphocytes measured by the subrenal capsule assay.

Lymphokine-activated killer cells (LAK) are able to kill natural killer (NK)-resistant fresh bioptic tumor cells. We have tried to increase the antitumor activity of peripheral blood lymphocytes by the simultaneous stimulation with interleukin-2 and autologous tumor extract (TE). The influence of LAK cells and LAK cells stimulated with TE was compared in the subrenal capsule assay in nude mice.

Stimulation of peripheral blood lymphocytes with autologous tumor and serum-derived fractions from patients with laryngeal carcinomas.

We investigated the in vitro stimulation of peripheral blood lymphocytes with tumor extracts and serum-derived fractions from five patients with laryngeal carcinomas. Lymphocyte cultures were propagated by Interleukin-2 or phytohemagglutinin. Sera of the same patients were fractionated and the amount of circulating immune complexes present was measured by a Raji cell assay.

Xenografting of nasopharyngeal carcinoma into athymic mice.

Four nasopharyngeal carcinomas (NPC) with positive Epstein-Barr virus serology were successfully grafted into athymic mice. Tumor growth could be maintained up to the 22nd passage. Strong similarity between original NPC biopsies and xenografts is demonstrated in terms of light microscopy and immunohistochemistry.

The expression of Ia-antigen on nasopharyngeal carcinomas xenografted into nude mice.

The expression of Ia-antigen on four different Epstein-Barr virus associated nasopharyngeal carcinomas xenografted into athymic mice could be detected by the monoclonal antibody OKIa. Xenografts of four additional head and neck tumors other than nasopharyngeal carcinoma and one xenograft of a metastatic melanoma cell line were negative for the Ia-antigen. Control antibodies OKT3, OKT4, OKT9, OKM1 and Leu7 were negative with all nasopharyngeal carcinomas and the non-nasopharyngeal carcinoma xenografts.