Escape of mouse mastocytoma P815 after nearly complete rejection is due to antigen-loss variants rather than immunosuppression.

Even though mastocytoma P815 often undergoes a nearly complete rejection in syngeneic mice, the tumor cells almost always escape to form progressive tumors. We found that this was not due to the establishment of an immunosuppressed state because genetically marked P815 cells, that were injected in mice where tumor escape was occurring, were readily rejected. An analysis of escaping tumor cell populations with anti-P815 cytolytic T lymphocyte (CTL) clones showed the presence of stable resistant variants. Using antigen-loss variants found in escaping populations or selected in vitro with CTL clones, we were able to define four different tumor-associated antigenic specificities, each recognized by a specific CTL clone. One of these specificities was absent from all escaping tumor cells and another had been lost by some of them.

Spinal lymphosarcoma and disseminated mastocytoma associated with feline immunodeficiency virus infection in a cat.

The course of naturally acquired infection with feline immunodeficiency virus was monitored in a cat over an 18-month period after diagnosis. The cat was admitted with diarrhea, poor body condition, a bite wound abscess, gingivitis, chronic fever, and splenomegaly. The cat's condition improved after splenectomy and remained stable for approximately 15 months, then began to deteriorate, as gingivitis, polyuria, polydipsia, pyrexia, multiple cutaneous masses, and hind limb paresis developed. The in vitro response of the cat's lymphocytes to mitogens was suppressed, and absolute lymphocyte counts were low. Spinal lymphosarcoma, disseminated mastocytoma, and presumptive diabetes mellitus were diagnosed after euthanasia. Decreased immune surveillance associated with feline immunodeficiency virus-related immunosuppression possibly played a role in the development of neoplastic disease in this cat.

Neutering dogs: effects on joint disorders and cancers in golden retrievers.

In contrast to European countries, the overwhelming majority of dogs in the U.S. are neutered (including spaying), usually done before one year of age. Given the importance of gonadal hormones in growth and development, this cultural contrast invites an analysis of the multiple organ systems that may be adversely affected by neutering. Using a single breed-specific dataset, the objective was to examine the variables of gender and age at the time of neutering versus leaving dogs gonadally intact, on all diseases occurring with sufficient frequency for statistical analyses. Given its popularity and vulnerability to various cancers and joint disorders, the Golden Retriever was chosen for this study. Veterinary hospital records of 759 client-owned, intact and neutered female and male dogs, 1-8 years old, were examined for diagnoses of hip dysplasia (HD), cranial cruciate ligament tear (CCL), lymphosarcoma (LSA), hemangiosarcoma (HSA), and mast cell tumor (MCT). Patients were classified as intact, or neutered early (<12 mo) or late (≥12 mo). Statistical analyses involved survival analyses and incidence rate comparisons. Outcomes at the 5 percent level of significance are reported. Of early-neutered males, 10 percent were diagnosed with HD, double the occurrence in intact males. There were no cases of CCL diagnosed in intact males or females, but in early-neutered males and females the occurrences were 5 percent and 8 percent, respectively. Almost 10 percent of early-neutered males were diagnosed with LSA, 3 times more than intact males. The percentage of HSA cases in late-neutered females (about 8 percent) was 4 times more than intact and early-neutered females. There were no cases of MCT in intact females, but the occurrence was nearly 6 percent in late-neutered females. The results have health implications for Golden Retriever companion and service dogs, and for oncologists using dogs as models of cancers that occur in humans.

Mast cell sarcoma of the scalp: the first sign of undisclosed systemic mastocytosis?

Mastocytosis is a neoplastic disease of mast cells and their CD34+ precursors, including a heterogeneous group of disorders. It is characterized by abnormal growth and accumulation of mast cells in one or more organ systems. Mast cell sarcoma is an extremely rare and aggressive disease characterized by local proliferation of atypical mast cells, destructive growth and poor prognosis, without systemic involvement. Very few clinical cases describing this entity have been reported in the literature. In this paper, we report a case of a mast cell sarcoma, localized in the scalp of a 63-year-old woman; it appears to be the first manifestation of undisclosed systemic mastocytosis.

Neoplastic transformation of mast cells by Abelson-MuLV: abrogation of IL-3 dependence by a nonautocrine mechanism.

Normal mast cells can be propagated in culture when medium is supplemented with interleukin-3 (IL-3). We demonstrate that Abelson-MuLV (Ab-MuLV) infection of mast cells eliminates dependence on IL-3 for growth. By contrast, Harvey, BALB, and Moloney MSV, which also productively infect mast cells, are unable to relieve IL-3 dependence. Ab-MuLV-induced IL-3-independent lines express the v-abl-specific transforming protein and have phenotypic characteristics of mast cells. These cells also possess high cloning efficiencies in soft agarose and are tumorigenic in nude mice. In addition, Ab-MuLV induces transplantable mastocytomas in pristane-primed adult mice resistant to lymphoid transformation, defining a new hematopoietic target for malignant transformation by this virus. None of the Ab-MuLV-derived transformants express or secrete detectable levels of IL-3 nor is their growth inhibited by anti-IL-3 serum. These results argue that Ab-MuLV abrogation of the IL-3 requirement is not due to an autocrine mechanism.

Systemic mastocytosis with extensive large cutaneous mastocytomas: surgical management.

A case of systemic mastocytosis is reported with an observation period of 20 years. During these two decades multiple manifestations of the disease appeared including urticaria pigmentosis, episodic histamine release, gastro-intestinal involvement and hepatosplenomegaly. The most extraordinary, and possibly unique phenomenon, has been the development of a massive proliferation of large mastocytomas mainly, but not exclusively, limited to the lower extremities. For different reasons (mechanical disability, bleeding, cosmesis), these tumors have required repeated admissions for surgical removal. The most successful technique has involved use of the ultrasonic scalpel.

Endogenous IL-12 is necessary for rejection of P815 tumor variants in vivo.

Although murine tumor cells have been transfected to express a multitude of different cytokines and shown to be rejected in vivo, it is unclear which of these factors might be useful to facilitate tumor Ag immunization schemes. A study of the normal immune mechanisms involved in tumor rejection when it naturally occurs should reveal critical signals for generation of antitumor CTL in vivo. The highly transfectable variant of P815, P1.HTR, was found to be rejected in the hind footpads by approximately one-third of syngeneic DBA/2 mice. Analysis of draining popliteal lymph nodes revealed a large influx of CD4+ and CD8+ T lymphocytes in all mice, indicating that a failure to reject was not due to the complete absence of an inflammatory response. However, although IL-2 and IL-3 were produced by lymph node cells from all mice, only approximately one-third generated a high IFN-gamma response. IL-4 was not detected. To explore a role for IL-12 in the induction of the IFN-gamma-producing phenotype, a histidine-tagged IL-12 fusion protein was expressed in mammalian cells and purified by nickel-chelate chromatography, and a rabbit antiserum was produced. Neutralization of IL-12 in vivo eliminated the high IFN-gamma response and prevented rejection of P1.HTR tumors and also of a more immunogenic tum- variant of P815, P198. Conversely, exogenous IL-12 delivered early during challenge with P1.HTR cells induced high IFN-gamma production and resulted in tumor rejection in most mice. Therefore, endogenous IL-12 is vital for the rejection of these tumors when it naturally occurs, supporting a role for exogenous administration of this cytokine to favor a Th1-like phenotype in the immunotherapy of cancer.