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Short- and long-term effects of a massive dose of 6-OH-DA upon marsh mice.

Single, sublethal subcutaneous doses of 6-hydroxydopamine (6-OH-DA) were given to young adult male and female Marsh mice. The ability of 6/8 males to sire 15 or more days later was not abolished. Of 10 females dosed during pregnancy, 6 failed to deliver and lost substantially in body weight. Of the 4 that delivered, 2 cannabalized their young. The offspring of the 6-OH-DA-dosed fathers and mothers showed no gross anatomical defects nor lessened survival rates. Confrontation of 6-OH-DA-dosed males with control males as pairs demonstrated increased anal sniffing as compared with control-pair confrontation. In a long-term series with males, liver anomalies including tumor development were demonstrated for 6-OH-DA. Lymphoid tumor induction was not affected. However, 3 local fibrosarcomas and 1 intrasorbital giant cell sarcoma arose. A sublethal dose of L-dopa had no lasting effect on male mouse aggression nor on other behavioral manifestations that would implicate 6-OH-DA formation as a metabolic route.

Aggression↗

[Augmentation of antitumor immune responses by the antitumor antibiotic bleomycin].

We investigated the augmentation of antitumor immune responses by the antitumor antibiotic, bleomycin (BLM). BLM augmented immune responses against tumor cells, such as transplantation resistance and tumor cell-neutralizing activity of spleen cells, in rats immunized with the tumor cells or bearing the tumor as a result of selective elimination of immune-suppressor cell activities. Moreover, BLM was able to activate macrophages as an effector of antitumor resistance. We observed good correlation between the therapeutic effects of BLM and the above immune augmentation when tumor-bearing rats were treated with the drug. These results suggest that the chemotherapeutic action of BLM partially depends on a host-mediated effect, i.e., antitumor immune responses augmented by the drug.

Adjuvants, Immunologic↗

Correlation between initial and long-term responses of spontaneous pet animal tumors to heat and radiation or radiation alone.

Most early-phase testing of new therapeutic modalities involves analysis of initial tumor response as opposed to estimation of long-term response. In this study, the validity of initial response rates to predict long-term responses was examined for tumors treated with radiotherapy alone compared with heat combined with radiotherapy. A total of 130 pet animals with either squamous cell carcinomas, melanomas, fibrosarcomas, mammary adenocarcinomas, or mast cell sarcomas were randomized to receive either radiation alone (XRT) or heat + radiation (delta + XRT). Responses to treatment were evaluated by response rates and response duration. The complete response (CR) rates were consistently higher for delta + XRT than for XRT across different histology groups. The combined therapy led to prolonged tumor response in all histological subgroups except melanomas, which had a longer response duration when treated with XRT alone (p = 0.043). This was in spite of a relatively high CR rate in that group (100% versus 12.5% for delta + XRT and XRT, respectively). In contrast, while no significant improvement in CR rate was observed for dermal squamous cell carcinomas treated with delta + XRT (XRT = 52.9%; delta + XRT = 68.8%), a significant improvement in response duration was noted (p = 0.002). These are two examples where CR rate did not predict long-term response. When all histological subgroups were combined (except melanomas), the CR rate was higher (p less than 0.001), and response duration was prolonged (p = 0.031) for delta + XRT compared to XRT alone.

Animals↗

Importance of minimum tumor temperature in determining early and long-term responses of spontaneous canine and feline tumors to heat and radiation.

A total of 130 dogs and cats with squamous cell carcinomas, melanomas, fibrosarcomas, mammary adenocarcinomas, or mast cell sarcomas were randomized to receive radiation (XRT) or heat plus XRT. Time-temperature data for each monitored tumor location were converted to degree-minutes or equivalent min at 43 degrees (Eq43). Response rates and durations of response were compared for subgroups of histology, volume, site, and heat treatment method. Thermal gradients existed in all heated tumors. The influence of these gradients on tumor response was examined by correlation of response with degree-minutes and Eq43 minima, maxima, averages, and ranges. A pattern emerged from these analyses linking dose minima, maxima, and ranges with prognostic subgroups as classified by volume, site, or treatment method. The data indicated that the coolest part of the tumor governed the biological response to combined heat + XRT. Tumors which received a minimum of 35 Eq43 had significantly longer durations of response than did those receiving XRT alone or less than 3 Eq43 (p less than or equal to 0.006 and 0.014, respectively; log-rank test). Furthermore, broad temperature ranges were associated with power-limiting "hot spots" and invariably led to underheating in other areas of tumor. Multivariate analysis found minimum Eq43 on the first treatment to be the best predictor of long-term response (p less than 0.05). Other biological covariates of site, volume, and histology contributed strength to the model, which was independent of Eq43 (p less than 0.05).

Animals↗

Isolation and preliminary characterization of an Adriamycin-resistant murine fibrosarcoma cell line.

A variant cell line (UV-2237-ADMR) resistant to the anthracycline antibiotic Adriamycin (Doxorubicin) was selected in vitro from the murine UV-2237 fibrosarcoma tumor cell line. Resistance to Adriamycin proved to be a stable characteristic of the UV-2237-ADMR line, whether the line was grown in vivo or in vitro. The UV-2237-ADMR line also exhibited increased resistance to N-trifluoroacetyladriamycin-24-valerate, daunorubicin, actinomycin D, amsacrine, mitomycin C, vinblastine, and vincristine but not to bleomycin. Cell-cell hybridization studies showed that the Adriamycin resistance is an incompletely dominant trait. Uptake and efflux studies with [14C]Adriamycin indicated that the resistance exhibited by the UV-2237-ADMR line was due to both reduced uptake of the drug and an increased active efflux.

Animals↗

[Sarcomas of the small intestine].

Four cases of sarcoma of the small intestine (2 leiomyosarcoma, 1 fibrosarcoma, and 1 Hodgkin's disease) are described. In each case, diagnosis was the outcome of surgery: emergency operation for acute abdomen in three cases (2 mechanical ileus, 1 perforation); exploratory laparotomy for recurrent haemorrhage following negative X-ray examination per os and clyster of the digestive tract on a number of occasions. The relevant literature is surveyed. Attention is drawn to the different anatomopathological and clinical forms, and to the difficulty of diagnosis.

Female↗

[Transplantable experimental tumor. Morphological and ultrastructural study (author's transl].

An experimental tumor which has been induced in newborn chicken, was transplanted into inbred BALB/c mice and then studied by the means of light and electron microscopy. Sendai virus fusion between MSV-H transformed rat cells and chickembryo cells provided the tumor. Histological pattern of this neoplasia seems to be superposable, both in chicken and in mouse, to that of anaplastic fibrosarcomas and shows some differences from either Rous sarcoma or BALB/c mouse H-6668 spontaneous rabdomyosarcoma patterns. tumor malignancy was evaluated onthe basis of rapid growth

Animals↗

International variations in the incidence of childhood soft-tissue sarcomas.

In the study of international childhood cancer incidence coordinated by the International Agency for Research on cancer, soft-tissue sarcomas comprised between 4 and 8% of all cancers between 0 and 14 years of age. Among predominantly white populations, the age-standardised annual incidence rate (ASR) for all soft-tissue sarcomas was between 5 and 9 per million. The most common histological subtypes were rhabdomyosarcoma (ASR 4-7 per million) and fibrosarcoma, including other malignant fibromatous tumours (ASR 1-2 per million). In the United States the incidence of rhabdomyosarcoma for black girls was only half that for white girls, while the rates for boys were similar in the two ethnic groups; fibrosarcoma had a higher incidence among black people than white people for both sexes. Throughout most of Asia, soft-tissue sarcomas almost invariably had a total ASR below 6 per million, rhabdomyosarcoma and fibrosarcoma again being the most common histological types. In Africa, incidence rates could not generally be calculated, but there were substantial numbers of registrations for rhabdomyosarcoma and fibrosarcoma. The majority of cases of Kaposi's sarcoma were in African children, and in eastern and southern Africa where Kaposi's sarcoma is endemic among adult men it comprised 25-50% of soft-tissue sarcomas and 2-10% of all childhood cancers; the sex ratio (M/F) was 2.2:1, in contrast to the overwhelming male predominance among adults. Variations between ethnic groups in the incidence of rhabdomyosarcoma and fibrosarcoma, together with their occurrence in a number of heritable syndromes, suggest that genetic predisposition is important in their aetiology. There was little evidence for an environmental aetiology in rhabdomyosarcoma and fibrosarcoma but an infectious agent may be responsible for childhood Kaposi's sarcoma.

Adolescent↗