Response to ionizing radiation of human bladder transitional cell carcinomas grown in the nude mouse.

The sensitivity to ionizing radiation of three human bladder transitional cell carcinomas grown in the nude mouse was investigated at four different radiation levels, 500, 1,000, 2,000 and 4,000 rad. Each tumor line exhibited a response pattern which reflected to a certain degree tumor differentiation and growth rate in the nude mouse. Exposure to 1,000 rad was the minimum amount of radiation required to produce a distinct, although transient, tumor response in all three tumor lines characterized by a growth delay of 3-4 weeks, whereas maximum tumor response was observed at the 4,000 rad radiation level. These studies would permit a better understanding of the behavior of human bladder cancer to ionizing radiation and may further facilitate efforts at identifying effective radiosensitizing agents that may result in maximizing tumor response.

Morphological, biological, and biochemical characteristics of human bladder transitional cell carcinomas grown in tissue culture and in nude mice.

The morphological, biological, biochemical, and karyotypic characteristics of four human bladder transitional cell carcinoma lines, SW-780, SW-800, SW-1738, and SW-1710, were investigated. In tissue culture, each cell line presented a distinct phenotypic expression. All but line SW-1710 grew when transplanted in the nude mouse. Light and electron microscopic studies showed morphological characteristics similar to the tumors of origin, being independent of the passages in tissue culture medium, tumor cell extracts, and the plasma of nude mouse-grown tumors, showing isoenzyme quantitative distribution typical for each cell line. In addition, each cell line exhibited a unique genetically determined enzyme phenotypic profile which, along with the karyotypic analysis, makes their identification feasible. These characteristics make the described tumor lines a valuable tool in studying various aspects of the biology of human bladder transitional cell carcinoma.

Establishment and characterization of human pancreatic adenocarcinoma cell line SW-1990 in tissue culture and the nude mouse.

A new tumor line derived from a human pancreatic ductal adenocarcinoma of a 56-year-old Caucasian male was established in tissue culture and the nude mouse. In tissue culture, the neoplastic cells grew as large, epithelial-like, mucin-producing cells. Injection s.c. of 1 X 10(6) cultured neoplastic cells into nude mice resulted in tumor formation histologically closely resembling the original neoplasm. Ultrastructurally, the neoplastic cells showed characteristics of ductal epithelium. The allozyme phenotypic profile of the line was established in 14 genetically determined loci, and chromosome studies showed a near-tetraploid pattern. Production of macromolecules such as lactate dehydrogenase and carcinoembryonic antigen were present in measurable amounts in culture media, tumor cell extracts, nude mouse-grown tumors, and the serum of tumor-bearing mice in amounts relative to tumor size. Pancreatic enzymes were not detected. These characteristics make tumor line SW-1990 a valuable tool in studying various aspects of the biology of human pancreatic cancer.

Human ciliary body epithelium in culture.

Human ciliary body epithelial cells have been maintained in vitro and have been partially characterized by the determination of growth rate, morphology, and ultrastructural parameters. The dissection technique employed allows the separation of pure ciliary body epithelium with a predominance of cells being from the nonpigmented layer. Growth curves indicate this cell population follows a prolonged rate of growth compared to other primary cell cultures. Loss of pigment granules noted by light microscopy were documented by morphometric analysis of electron micrographs. Thirty-two percent of the cultures attempted were successful. Maintenance of these cells in vitro may provide a means for studying their enzyme systems, growth factors, reactions to various stimuli, and the effects of this cell population on other intraocular tissues.

Histopathologic evaluation of response to treatment of human tumors grown in the nude mouse.

The histopathologic changes following chemotherapy treatment of a number of human tumors grown in nude mice were evaluated. On the basis of the histopathologic profile, three response levels were recognized--a mild response, a moderate response and a severe response. Severe response was characterized by arrest of cell division and profound nuclear-cytoplasmic degenerative changes. Regrowth of effectively treated tumors originated in clusters of cells most probably representing resistant tumor cell clones. Histopathologic changes represent a sensitive indicator of the response of nude mouse grown human tumors to anticancer agents. Availability and correct interpretation of the post-treatment histopathologic picture is of importance in selecting the proper combination treatment which would maximize tumor response.

Hemolytic anemia associated with leptospirosis. Morphologic and lipid studies.

A case of fulminant hemolytic anemia associated with a leptospiral infection is presented with morphologic and erythrocyte lipid studies. Both the frequency and pathogenesis of anemia in human leptospirosis is poorly understood. The anemia frequently observed in Weil's syndrome has been ascribed on clinical impression to blood loss, renal failure, and/or an ill-defined hemolytic process. However, hemolytic anemia associated with leptospirosis in animals is well documented and is due to hemolysins with phospholipase activity. Our patient's erythrocyte morphologic abnormalities on bright light and electron microscopy included particles of cells and cells with a thorny or spiculated surface suggesting that the hemolytic process was due to membrane injury. Measurement of the erythrocyte membrane lipids showed reductions in sphingomyelin and phosphatidylethanolamine suggesting that the observed hemolysis and morphologic changes resulted from phospholipases produced by the infecting leptospirae.

Biological behavior of human malignant tumors grown in the nude mouse.

The biological behavior of a number of nude mouse-grown human epithelial tumors of different histogenetic background was studied. They included three transitional cell carcinomas and a mucin-producing carcinoma of the urinary bladder, two pancreatic adenocarcinomas, a colon adenocarcinoma, a breast ductal carcinoma, and an epidermoid carcinoma. Microinvasion was a constant finding in all tumors examined. All but one of the tumors studied showed macroinvasion and metastases. Tumors transplanted s.c. in the anterior aspect of the lateral thoracic wall metastasized primarily to the regional and mediastinal lymph nodes. In certain cases, systemic metastases were observed affecting the submaxillary, contralateral axillary, and inguinal lymph nodes. Lung metastases occurred through the lymphatic and hematogenous routes. It is concluded that the nude mouse-grown human tumors investigated in the present study show overt malignant behavior recapitulating the biological characteristics of the tumor of origin.

T lymphocytes in children with allergic respiratory disease.

The role of T lymphocytes in atopic disease is of considerable importance because animal studies indicate that cells of this lymphoid series may influence reaginic antibody response. T lymphocyte subpopulations were studied in a group of 76 children with allergic respiratory disease. There was no statistical difference between atopic children with asthma and those with allergic rhinitis as compared with an age-matched control population of 20 non-atopic children in terms of levels of active T lymphocytes or total T lymphocytes. The results of this study do not support the concept of a T cell immunodeficiency in children with allergic respiratory disease.

Morphologic and immunologic studies of a human colon tumor cell line (SW-48).

A permanent human tissue culture cell line (SW-48) has been established from an adenocarcinoma of the transverse colon. Cells in the center of early colonies were cuboidal and loosely bound; cells on the periphery of the same colonies were more columnar, the nuclei were displaced toward the basal region, and the free surface formed stunted microvilli. These columnar cells ofter aligned themselves to resemble normal absorptive tissue. Carcinoembryonic antigen (CEA) was identified by immunofluorescent microscopy on the surface membrane of the tumor cells. Significantly more CEA could be isolated from the culture medium than from the whole cells. On agar gel diffusion analysis with a monospecific anti-CEA serum (G.P. 32), SW-48 CEA and CEA preparations from solid tumors demonstrated complete identity.

Classification of human colorectal adenocarcinoma cell lines.

Eleven human colorectal adenocarcinoma cell lines established in this laboratory were classified into three groups based on morphological features (light and electron microscopy), modal chromosome number, and ability to synthesize carcinoembryonic antigen (CEA). Group 1 cell lines contained both dedifferentiated and differentiating cells growing in tight clusters or islands of epithelium-like cells; their modal chromosome number was about 47, and they synthesized small to moderate amounts of CEA. Group 2 cell lines were more dedifferentiated, were hyperdiploid, and synthesized small amounts of CEA. Group 3 cell lines were morphologically similar to those of Group 1 by light microscopy. They differed ultrastructurally by containing microvesicular bodies; the modal chromosome number varied from hyperdiploid to hypertriploid or they had bimodal populations of hypodiploid and hypertriploid cells, and they synthesized relatively large amounts of CEA. No correlation could be found between Broder's grade or Duke's classification of the original tumor and modal chromosome number or ability to synthesize CEA. These findings support Nowell's hypothesis that the stem line is different for each solid tumor, which makes it difficult to relate chromosomal changes to the initiation of the neoplastic state.