Engraftment of human tumor-infiltrating lymphocytes and the production of anti-tumor antibodies in SCID mice.

We report here the placement of nondisrupted 1-mm3 pieces of fresh human lung tumor biopsy tissue into the subcutis of severe combined immunodeficient (SCID) mice results in the engraftment of tumor-infiltrating leukocytes (TIL) in all but 5 of 148 mice inoculated with 39 different biopsy tissue specimens. In mice coengrafted with tumor and TIL the normal histologic architecture of the tumor and TIL interface was maintained for up to 22 wk. The TIL in the xenograft were shown to divide and were maintained exclusively at the site of tumor inoculation.

Consistent hepatic metastasis of human colorectal cancer in severe combined immunodeficient mice.

A major stumbling block in the study of human colorectal cancer metastasis has been the lack of an effective in vivo model producing liver metastasis on a consistent basis. In this study surgical specimens of colorectal carcinoma were implanted in scid mice and studied for engraftment, growth, and the capacity to produce hepatic metastases. Human colorectal cancers would engraft and propagate in the subcutis and intraperitoneally.

Human villous adenomas engrafted into scid mice survive for prolonged period without malignant transformation.

Human villous adenomas are thought to represent premalignancies that subsequently give rise to colorectal adenocarcinomas. Currently there is no in vivo model in which to study the dedifferentiation and malignant transformation of these tumors. We establish here that human villous adenomas can be successfully engrafted into severe combined immunodeficient (scid) mice.

Clones of tumor cells derived from a single primary human lung tumor reveal different patterns of beta 1 integrin expression.

Previously we reported that over 75% of human non-small cell lung cancers overexpress the beta 1 integrin VLA-2 on their surface and show an increase in the mRNA encoding the alpha-2 chain of this integrin. These results suggested the possibility that the overproduction and overexpression of one or more of the beta 1 integrin may be involved in the pathogenesis of human lung tumors by modulating the invasive and/or metastatic potential of the tumor. We report here the generation and characterization of multiple clones of tumor cells derived from the primary culture of cells obtained from biopsy tissue of an aggressive human squamous cell lung tumor.

Human lung tumor cell secretion of interleukin-2 for protection against tumor engraftment.

Background: Lung cancer continues to claim large numbers of human lives each year despite advances made in conventional therapies. The use of biologic response modifiers to modulate the immune system against human tumors is an alternate form of immunotherapy. Interleukin-2 (IL-2), or T-cell growth factor, is an important modulator of activated T cells.

Arrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes.

Incorporation of polyethylene glycol-derivatized phospholipids into liposomes results in carriers that can enhance the therapeutic efficacy of encapsulated drugs by imparting the ability to evade the reticuloendothelial system and remain in the circulation for prolonged periods. In this study, doxorubicin encapsulated in these sterically stabilized liposomes (S-DOX) is shown to completely arrest the growth of human lung tumor xenografts in severe combined immunodeficient (scid) mice. Doxorubicin administered at equivalent doses as free drug or encapsulated into conventional liposomes was ineffective at completely arresting the growth of this human tumor, although a decrease in tumor growth rate compared to untreated controls was observed.

Antitumor response independent of functional B or T lymphocytes induced by the local and sustained release of interleukin-2 by the tumor cells.

Transfection of tumor cells with a vector containing the entire coding sequence of human interleukin-2 (hIL-2) was previously shown to convert the tumorigenic murine fibrosarcoma line CMS-5 into a non-tumorigenic line. The failure of the IL-2-secreting tumor to grow in conventional (immunocompetent) mice was attributed to the activation of CD8+ T cells that exhibited tumor specificity and memory. In order to determine whether or not the IL-2 produced by the tumor may be activating tumor cytotoxic effector cells other than B or T cells we have repeated this study using immunodeficient SCID and SCID-beige mice as syngeneic tumor recipients.

The study of human neoplastic disease in severe combined immunodeficient mice.

Experimental models of human neoplastic diseases are used in attempts to reconstruct events that occur in patients with cancer. Although in vitro systems provide a wealth of information about the cellular and molecular biology of tumor cells, they are inadequate for studies that address the complexities of human neoplasia pertaining to metastasis, experimental therapeutics, and immunity. Since the late 1960s, athymic nude mice have provided an opportunity to study the growth and, in some cases, the metastasis of xenografted human tumors in vivo.

Retrotracheal goiter.

Retrotracheal extension of a goiter, though rare usually causes respiratory compromise, dysphagia or vascular obstruction. We have described an asymptomatic patient with a large retrotracheal goiter resected via a collar incision.

Angiosarcoma of the axillary vein.

Angiosarcoma is a malignant tumor of vascular origin. Malignant primary vein tumors are rare. The case of a 64-year-old patient who underwent a left forequarter amputation for angiosarcoma arising from the left axillary vein, a site not previously described, is presented.