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Transplantation of Human Tumors Into Cortisone-Treated Hamsters*

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Transplantation of Human Tumors Into Cortisone-Treated Hamsters* Transplantation of Human Tumors into Cortisone-treated Hamsters* W. BRADFORDPATTERSON,!ROSANNAN.CHUTE,ANDSHELDONC.SOMMERSA (Cancer Research Institute, New England Deaconess Hospital, Boston 15, Mass.) The desirability of obtaining living human for animals weighing less than 75 gm. and 2 mg. malignant tissue for experimental purposes con for those over this weight, was given subcutane- tinues to grow in proportion to our increasing ously 3 times a week starting on the day of im knowledge of the genesis and treatment of cancer. plantation. Tumors were obtained fresh from the Although several methods for growing human operating room and transplanted as rapidly as cancer outside of the primary host have been de possible. The total time required for this process scribed and utilized (7-10, 13), human tumors varied from 30 minutes to 3 hours. Frozen sections which can be grown in predictable amounts, with were prepared in most instances, and care was in a reasonable time, and by different investigators taken to select fragments of tumor free of necrosis in laboratory animals, have not been reported. and gross infection. The tissue was not, as a rule, However, from the work of Toolan (14) it can be sterile on receipt, and no effort was made to steri surmised that after 70 years of effort the tools and lize it. However, sterile instruments were used, knowledge are at hand with which permanent fragments from within the received tissue were and useful heterotransplantation may be accom selected, and the recipient site was gently and plished. briefly cleansed with Zephiran (1:1000). The tis The purpose of this paper is to report a human sue was kept on a sponge wet with saline while epidermoid carcinoma, now established in cor fragments roughly 1-2 mm. in diameter were cut tisone-treated hamsters, which shows every evi and placed in No. 18 trocars. Transplantation dence of possessing sufficient "growth potential" was performed with the animal under intraperi- to continue as a permanently transplantable tu toneal nembutal anesthesia, depositing the tumor mor, growing with sufficient rapidity and certain near the tip of the everted cheek pouch. The ty to make it of value for experimental use. This pouch was handled as little as possible in order to tumor is one of a series of 37 human neoplasms minimize trauma and reaction. Animals having transplanted in the past 7 months. Histological tumor transplants were anesthetized every 5—7 sections are available in 33 of these cases, verify days for inspection of the pouches. Transplants ing "survival" in 23, or 70 per cent. were made to both cheek pouches. On a few oc casions, two or three fragments rather than one MATERIALS AND METHODS have been placed in each pouch. This has had no The hamster cheek pouch technic described by apparent effect on the growth or failure of the Lutz et al. (11) was selected for use because of its transplant. promise as a simple method with easily observa Transplants have been removed for study by ble results. Golden hamsters of both sexes, 3-5 everting the cheek pouch and excising part or all weeks old (40-70 gm.) were used. They were ob of the tumor. Sterile technic was used if the ani tained from a local professional breeder. A num mal was not to be sacrificed. Hemostasis was ob ber of older animals have been employed for par tained by brief local pressure. Healing of the mu ticular experiments. They were fed Purina Labo cosa is definitely retarded by treatment of the ratory Chow and water ad libitum, with lettuce hamster with cortisone, but a small mucosal rent provided once a week. Cortisone acetate, 1 mg. is well tolerated in an otherwise unaffected pouch. * This work was supported by funds from the American Partial removal of the transplant is often followed Cancer Society and United States Atomic Energy Commission by local infection, which may subside without Contract AT(SO-1)-901 with the New England Deaconess Hos treatment or become invasive. pital. t Fellow in Cancer Research of the American Cancer So A few transplants have been biopsied within ciety. Present address: Peter Bent Brigham Hospital, Boston, the 1st week, but those utilized in calculating tu Mass. mor survival statistics were all at least 12 days ÃŽPresent address : Massachusetts Memorial Hospitals, old. Specimens for histological examination were Boston, Mass. placed in Zenker's fixative and stained with Received for publication May 14, 1954. hematoxylin-eosin. 656 Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 1954 American Association for Cancer Research. PATTERSONetal.—Transplantation of Human Tumors into Hamsters 657 RESULTS repetitive, frequent transplantation. Two other Table 1 lists the results of this series. The usual tumors, to be discussed in a later paper, one epi- transplant shows a two- or threefold increase in dermoid and one embryonal carcinoma, also size in the 1st week, with slight increase in vas- promise to be permanently transplantable. "Deac-l."—This tumor originated in the pa cularity. The enlargement may be due to any one of several factors; there may clearly be growth of rotid gland of a 74-year-old man. The pathologi the tumor, with little host reaction except for an cal diagnosis was muco-epidermoid carcinoma, enlarging vascular supply; the existing tumor grade II (Fig. 3). It was implanted in both cheek cells, if glandular in function, may produce a pouches of six hamsters within 30 minutes of its sizable amount of secretion; a host reaction of removal from the patient, and four of these ani inflammatory exúdate, edema, and hemorrhage mals were treated in the standard fashion with may develop in spite of treatment with cortisone. TABLE1 We feel some confidence now in distinguishing these reactions grossly. Growing tumors invari SURVIVALOFHUMANTUMORTRANSPLANTSIN ably have a healthy pink color, shading to blue CORTISONE-TREATEDHAMSTERS according to their intrinsic vascularity. The Cases Positive* Negative borders are sharp, and there is no gross evidence Adenocarcinomas: 1 Parotid 0 of host reaction. Mucinous secretion has been Lung 1 recognizable as such in and around a few trans Breast o Pancreas 0 plants. On the other hand, the presence of a mud Sigmoid 0 dy and variegated coloring with indistinct borders Endometrium 0 indicative of edema is invariably associated with Prostate 0 a considerable host reaction. In such transplants Carcinoma simplex (breast) there may be a large portion of viable tumor cen Epidermoid carcinomas: 0 7 e Mouth 1 0 1 trally, but progressive growth does not occur. In Esophagus 1 1 o short, if the host can react to an appreciable ex Lung 3 3 0 tent, it usually wins. Grossly infected transplants Renal pelvis 1 1 I) Vulva 1 1 0 have dead-white or yellow areas indicating ab Penis 1 1 I) scess formation. Treatment with cortisone is ap Mixed tumor of parotid 2 •i 0 parently responsible for elimination of the marked Undifferentiated (scalp) 1 \ 0 granulomatous reaction which in earlier experi Carcinoid (liver) 1 \ o Seminoma (testis) 1 0 1 ments (1) was difficult to distinguish from viable Small-cell carcinoma (lung) 1 0 1 tumor. Embryonal carcinoma (testis) 1 1 0 The growth period may last from 1 to 3 weeks, Fibrosarcoma (shoulder) 1 1 0 Lymphocytoma 1 I) 1 and in some cases is followed by partial or com Glioblastoma (brain) 1 0 1 plete regression during the ensuing days or weeks. Basal-cell carcinoma 1 1 0 A few transplants show initial growth, then sta Giant-cell tumor (spine) 1 1 0 bilization and persistence for long periods of time. Totals: 88 23 10 One carcinoma of the breast (Fig. 1) has recently * Histologie evidence of cell survival and/or growth for a period of at least lìdays. Microscopic sections demonstrating questionable survival of been transplanted to a second generation of ham only a few cells were classed as negative. sters after surviving in the original animal for 116 days. This tumor showed many of the char cortisone. From the start the tumor showed ex acteristics of growth reported for anterior chamber ceptional growth, as evidenced by rapid and transplants (3, 6); that is, it grew initially for a marked increase in size and vascularity of five period of 4 weeks and then regressed. After an of the transplants. After 14 days in the first-gen interval of 6 weeks, during which time another eration animals, four tumors were large enough breast carcinoma was implanted and failed to to permit another transplantation. This process grow in the same pouch, the original nodule slowly has now been repeated to the 16th generation in enlarged tenfold. Biopsy at the time of the second the course of 9 months. In view of the marked transplantation showed a healthy, slowly growing increase in total mass of tumor now available, carcinoma (Fig. 2). Microscopically, it is difficult there seems little reason to anticipate a reversal to differentiate this from a tumor which shows of form and loss of the tumor. only "persistence," but in view of the substantial These transplants have an initial latent period increase of the gross tumor mass, proliferative of from 4 to 15 days, followed by an increase in growth has very obviously taken place. the vascular supply to the tumor and then steady The tumor to be described below is one of the enlargement. The tumor maintains a healthy series showing the striking growth which permits pink color, a firm consistency, and a well-vascu- Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 1954 American Association for Cancer Research. 658 Cancer Research larized surface. No detailed studies on growth cortisone treatment.
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