Grant Taylor

The Quest for Human Cancer Viruses. A New Approach to an Old Problem reveals Cancer Induction in Hamsters by Human Adenovirus.

A new approach to the important but difficult task of revealing possible human tumor viruses has been presented in this article. By systematic testing of already known human viruses for oncogenic properties, it was found that in hamsters injected intrapulmonarily with tissue culture fluid of human type 12 adenovirus within 24 hours after birth there was a very high incidence of malignant tumors at the site of injection in from 1 to 3 months. The tumorinducing activity was not lost by filtration through Selas 02 filters or by tissue culture passages in HeLa cells. Tumors thus induced grew in, and killed, a high percentage of the unconditioned young adult hamsters into which they were transplanted. No such tumors occurred in hamsters injected with control tissue culture fluid or with culture fluids of the other viruses tested, or in control breeder hamsters. The possibility that contamination with polyoma virus and simian virus 40 might be responsible for the tumors induced was specifically excluded by a variety of tests. The possible involvement of still other, as yet unknown, contaminant viruses was excluded by a positive association of the tumor-inducing ability with the adenovirus content. Of eight human sera tested, only those four which neutralized the adenovirus-type cytopathic effect also neutralized the tumor-inducing effect. Of 700 human sera tested, 26 percent contained CPE-neutralizing antibodies for type 12 adenovirus at titers of 1:4 and higher (23).

Cancer Induction in Hamsters by Human Type 12 Adenovirus. Effect of Age and of Virus Dose.

Summary The susceptibility of newborn hamsters to induction of sarcomas at the site of injection of human type 12 adenovirus decreases rapidly with increasing age at time of injection. For a given age at the time of injection, the incidence of tumors induced is directly proportional to the dose of virus injected. The 50% tumor-inducing dose in hamsters injected when less than one day of age lies between 0.5 and 50 MTCID100 of adenovirus under the conditions of these experiments. Increasing the dose of virus to 1000 MTCID100 produced one tumor among 8 hamsters injected as late as 14 days of age, but none in 3-week or older hamsters.

Intensive chemotherapy and radical resections for primary nonseminomatous mediastinal germ cell tumors

BACKGROUND Primary nonseminomatous germ cell tumors of the mediastinum (PNSGM), unlike malignancies of gonadal origin, have a poor prognosis. We report a single institutional experience over a 5-year period of PNSGM treated with intensive chemotherapy, followed by radical operation in those who responded to this neoadjuvant regimen. METHODS From 1993 to 1998, 20 patients were referred for the management of PNSGM. All were male, with a median age of 30.5 years (range 18 to 48). Eighteen of 20 (90%) presented with symptoms. Most tumors were large, with a median diameter of 10 cm (range 3 to 20 cm). Thirteen patients (65%) had metastatic disease at the time of presentation. Eleven patients had received no prior treatment (initial group) and 9 were referred for salvage therapy after progression of their tumors, following treatment at other facilities (salvage group). All had elevated serum tumor markers (beta hCG and alpha-fetoprotein). Preoperative chemotherapy included alternating cycles of combinations of 3 or more drugs, including cisplatin, bleomycin, etoposide, vincristine, methotrexate, actinomycin, cyclophosphamide, and doxorubicin. An average of 10 cycles of chemotherapy was given to each patient in the initial group, and six to those in the salvage group. Five patients (25%) developed transient renal insufficiency, and 35% developed pulmonary infiltrates related to bleomycin. There were 3 chemotherapy related deaths. RESULTS After chemotherapy, 11 patients underwent operation, with 10 complete resections of the residual mediastinal tumors. There were no perioperative deaths. The 2-year survival in the initial group is 72%, and 42% for the salvage group. CONCLUSIONS An aggressive, multidisciplinary approach of alternating cycles of chemotherapy, followed by complete surgical resection of all remaining disease in patients whose markers normalize, can be associated with prolonged survival in patients with PNSGM.

l-Phenylalanine mustard as a treatment for metastatic osteogenic sarcoma in children

Seven children with metastatic osteogenic sarcoma have been treated with the chemotherapeutic agent, l -phenylalanine mustard (PAM). The pulmonary metastases of one patient have shown striking regression for a period exceeding six months. Transient regression of the tumor was observed in a second patient. Self-limited marrow aplasia occurred in these 2 patients and in a third patient whose tumor failed to regress. The toxic dose for the bone marrow and the therapeutic dose for osteogenic sarcoma appear to be similar. Use of the agent necessitates careful hematologic surveillance and an awareness of the possibility of delayed toxicity.

Cancer Induction in Hamsters by Human Type 12 Adenovirus. Effect of Route of Injection.

Summary Tumors were induced at the site of injection of human type 12 adenovirus into newborn hamsters by each of the intrapulmonary, intrapleural, intraperitoneal, intravenous and subcutaneous routes, leading to death within 29 to 108 days. Whereas at higher doses of virus the subcutaneous route of injection was as effective as the other routes, at lower doses of virus it appeared less effective. For the intracranial route of injection, no local tumors were observed but one such hamster developed multiple abdominal tumors, and 3 developed hydrocephalus. Of 35 hamsters with tumors at the site of injection by various routes, remote tumors in the liver also developed in 10. Similar liver tumors were also found in 4 intravenously injected hamsters without a tumor at the site of intravenous injection. Of 7 hamsters administered virus by intranasal instillation, none have died of tumors in approximately 9 months to date.

Characteristics of Human Adenovirus Type 12 Induced Hamster Tumor Cells in Tissue Culture.

Summary Characteristics of a human adenovirus type 12 induced hamster tumor serially propagated in vitro are described. These include small cell size, epithelioid appearance, rapid growth rate, resistance to superinfection with A-12, and transplantability to weanling hamsters. These cells grew either as monolayers or as balls of aggregated cells detached from the glass, depending on whether calf serum or horse serum was added to the Eagles medium. Attempts to demonstrate virus activity by subculture of supernatant fluids and lysed cells into HeLa cells, mixed culture with human and hamster cells, electron microscopy, and inoculation of newborn hamsters with irradiated tumor cells were negative.

Persistent Infection of Human Cells (HeLa) with Adenovirus Type 12.

Summary The establishment of an adeno-virus type 12 cell carrier system is described. Characteristics of the carrier cultures include an initial dependence on inhibitor or antibody in human serum, an enhanced rate of growth after the fifth day as compared to uninfected cells, a relatively high percentage of infected cells, but a low percentage of detectable virus yielding cells, and relative resistance to super-infection. Secondary mechanisms responsible for the carrier state may include the selection of resistant cells, interference by non-infectious virus and inter-feron.

Treatment of acute leukemia:current results, and analysis of what we can do now

The years since World \\ar II have wit nessed a progressive increase in medical con em-ru in the care and treatment of acute leu kern ia in children. In keeping @vi th til is (†̃oncern,periodic assessments of progress are important. This report is based on a partial survey of the literature on acute leukemia an(l represents an attempt to quantitate tile relative effectiveness of tile ehernotiierapc-imtic agents currently used during the treatment @iftIns disease.