Comparative Studies of Normal, ‘Spontaneously’ Transformed and Malignant Human Urothelium Cells In Vitro

CHE Ni OT'HERAPY

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rnay be a 2tdditicnal benefit to paoratory of 1\/aticnal Institute and Diseases, }lational Institutes of tients who do not to conventional endocrine lation. The National Prostatic Cancer Project has embarked on a prospective randomized clinical trial 600) to Eur. J. Cancer C!in. 19: 757-773 (June) 1983 assess the efficacy of adding chemotherapy to hormonal therapy The discovery of T cell growth factor (or interleukin-2) in for treatment of patients with metastatic carcinoma of the supernatants of lymphoid cells stimulated with lectins or antiprostate. The 188 patients studied with advanced but stabilized dis- gens has allowed for production of large quantities and even seminated prostatic cancer after 3 months of hormone therapy monoclonal lines of T cells with cytotoxic helper or suppressor were randomized to 1) diethylstilbestrol, 2) diethylstilbestrol activity. Using human and murine cells major efforts have been plus cyclophosphamide or 3) diethylstilbestrol plus estramus- made during the last 3 years to develop cytotoxic lymphoid cell tine phosphate. Of these 188 patients 161 were evaluated for lines with antitumor reactivity in the hope of applying such objective response to therapy after 68 months. Objective re- reagents in adoptive immunotherapy of cancer. T cells sensisponse rates, prolonged survival or prolonged response dura- tized specifically to normal alloantigens or to tumor antigens tions were not detected among these groups. However, relief of and expanded subsequently with T cell growth factor have been pain was greater in patients who received chemotherapy plus shown to maintain their specific cytotoxic reactivity to some hormone therapy than in those who underwent orchiectomy degree during a long interval. Recent studies in mice already have indicated that T cell growth factor-propagated cytotoxic and diethylstilbestrol. N J. cells also can exert some therapeutic effects in vivo. 3 figures, 9 tables, 22 references Peripheral blood lymphocytes from 38 normal donors and 27 cancer patients were propagated in bulk cultures for 3 to 6 Methotrexate and Mitomycin for Patients With Meta- weeks using T cell growth factor. In addition, cultures derived static Transitional Cell Carcinoma of the U irinary from lymphocyte preparations enriched for or depleted of natT.ract ural killer cells and several clones of cultured cells were studied. I. F. TANNOCK, Departments of Medicine and Medical Biophys- The following main observations were made: 1) peripheral ics, the Ontario Cancer Institute and Princess Margaret Hos- blood lymphocytes of patients and healthy donors could be expanded to large numbers (up to 2,500-fold), 2) cytotoxic pital, Toronto, Canada lymphoid cells derived from unfractionated peripheral blood Cancer Treat. Rep., 67: 503-504 1983 lymphocytes exhibited intermediate levels of cytotoxic Methotrexate is known to have activity against metastatic against autologous and allogeneic fresh lung tumor cells, and transitional cell carcinoma. The author reported previously a strong cytotoxicity toward several cultured adherent tumor 39 per cent response rate in 38 patients with measurable disease cells, 3) cultures originated from populations enriched for nattreated with the combination of methotrexate, doxorubicin and ural killer cells were highly cytotoxic against adherent tumor cyclophosphamide. Unfortunately, several of the patients ex- target cells and against a natural killer cell-sensitive leukemic perienced severe mucositis and/or nausea and vomiting. Mito- cell line (K562), while cultures derived from populations demycin had been reported to give a response rate of approxi- pleted of natural killer cells preferentially were cytotoxic to mately 20 per cent when used to treat metastatic transitional adherent target cells, 4) clones of cytotoxic lymphoid cells also cell carcinoma. It also seems effective against superficial disease were strongly cytotoxic but 2 of 3 clones tested showed a when instilled into the bladder. Because methotrexate and narrower spectrum of target than that of uncloned mitomycin cause little nausea and vomiting compared to com- cytotoxic lymphoid cells, and 5) when mixed with 2 carcinoma binations containing doxorubicin or cisplatin, the author eval- cell lines cytotoxic lymphoid cells were able to inhibit tumor uated the combination of methotrexate and mitomycin in pa- growth in nude mice. W. W. H. tients with metastatic transitional cell carcinoma. 4 figures, 9 tables, 46 references Methotrexate and were given to 16 patients with metastatic transitional cell carcinoma who had received no Studies of S,101~bu1,2n11!¾h1' T:ransprior chemotherapy. A total of 5 achieved a partial formed and Malignant Human Urothelium Cells In response with the median duration of 3 months (range 3 to 8 Vitiro months) but the trial was abandoned because of severe toxic ,-,~u,~uvc

effects in 6 of the 16 patients. This combination appears to be more toxic and no more effective than methotrexate alone. W.W.H. 1 table, 8 references

Antitumor Reactivity In Vitro and In Vivo of Lymphocyte§ From Normal Donor§ and Cancer Patients Propagated i.n Culture With T Cell Growth Factor (TCGF) E.

B. L. IKEJIRI, T. TIMONEN, G. D. BONNARD, J. J. NAVARRO, B. SREDNI AND R. B. HERBERMAN, Laboratory of Immunodiagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, Transplantation Research Branch, Naval Medical Research Institute, Bethesda, Maryland, Department of Hematology, Portsmouth Naval Medical Center, Portsmouth, Virginia and LabKEDAR, REID, N.

Copenhagen and Department of Pathology, K0benhauns Amtssygehus, Herlev, Denmark, Department of Urology, Huidoure Hospital, Copenhagen, Denmark, Department of Urology, K0benhavns Amtssygehus, Herleu, Denmark and Department of Pathology, Finsen Institute, Copenhagen, Denmark Eur. J. Cancer Clin. OncoL, 19: 775-789 (June) 1983 The urothelium-derived cell lines described in this report were established for use in a series of immunological investigations. Similar lines have been propagated in other laboratories. However, bladder cell lines propagated in vitro vary markedly in morphology, chromosomal number, growth pattern, differentiation and sensitivity to cell-mediated cytotoxicity. There-

184

ONCOLOGY AND CHEMOTHERAPY

fore, use of such cells in in vitro immunological tests necessitates a detailed analysis and classification. The authors reported previously studies of the sensitivity of a number of their cell lines to natural cytotoxicity, their human leukocyte antigen expression, and ability to invade and destroy normal tissue in vitro. In the current study, which includes 13 human bladder cell lines of nonmalignant or malignant origin, a comparison was made of morphology, chromosomal mode, growth fraction and tumorigenicity in nude mice. Signs of apparently spontaneous transformation were seen in 2 cell lines of nonmalignant origin. The possibilities for cross-contamination as an explanation of these signs of spontaneous transformation are discussed. During these studies radiation-dependent cytotoxicity of disposable microtissue culture plates was revealed as another important source of error. W. W. H. 8 figures, 4 tables, 40 references

Neuron-Specific Enolase in Neuroendocrine Tumors of the Thymus, Bronchus, and Skin M. R. WICK, B. W. SCHEITHAUERAND K. KOVACS, Department of Surgical Pathology, Mayo Clinic, Rochester, Minnesota, and Department of Pathology, University of Toronto, St. Michael's Hospital, Toronto, Ontario, Canada

Amer. J. Clin. Path., 79: 703-707 (June) 1983 Despite recent dissatisfaction with the concept of a neuroectodermally derived Amines Precursor Uptake and Decarboxylation (APUD) system in mammalian endocrine tissues, the pathologic features of various tumors originating from such tissues have sufficient similarities to support their classification as a distinctive neoplastic group. The enzyme neuron-specific enolase is present in neurons of the central and peripheral nervous systems, in normal neurotactile cells of the skin and in selected neuroendocrine neoplasms. Tissues and tumors that are not neural or APUD in derivation lack this isoenzyme or show extremely low activities. Staining was positive for this enzyme in specimens from 11 patients with thymic carcinoid tumors, 3 with bronchial small cell carcinomas (all with cutaneous metastases) and 10 with trabecular carcinomas of the skin. The authors concluded that while the presence of this neuron-specific enolase is highly suggestive of a neuroendocrine differentiation, this marker should not be used as a sole indicator of such differentiation in the absence of other morphologic or immunohistochemical evidence. For reasons yet unclear, there have been definite false negative results, as indicated in the current study, and in an unpublished report the authors noted an 11 per cent incidence of (?) false positive test results in nonneural endocrine neoplasms. P. M. H. 6 figures, 1 table, 21 references

Radiographic and Scintigraphic Skeletal Imaging in Patients With N euroblastoma: Concise Communication M. BAKER, A. R. SIDDIQUI, A. PROVISOR AND M. D. COHEN, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana

J. Nucl. Med., 24: 467-469 (June) 1983 Bone and bone marrow scans, and radiographic skeletal surveys were reviewed in 40 children with neuroblastoma. Knowledge concerning metastasis is important in children with this disease. The authors found that the most sensitive assay

was the bone scan, which yielded few false negative results. In fact, a positive skeletal survey and a normal bone scan were found in 1 child but this was performed in only 10 children. The authors recommended that routine screening should be done by bone scan alone and that a skeletal survey should be done only when major therapeutic decisions are contemplated, such as additional surgery. Lastly, bone marrow scans can be helpful in the same group of individuals, since of 42 bone and bone marrow scans performed over-all, abnormal bone marrow scans and normal bone scans were found in 3 children. C.L.P. 2 tables, 8 references

Metastatic Cancer From an Undetermined Primary Site

J. A. GREAGER, D. WOOD AND T. K. DAS GUPTA, Division of Surgical Oncology, Department of Surgery, University of Illinois at the Medical Center, Cook County Hospital, VA West Side Hospital, and the Hekteon Institute for Medical Research, Chicago, Illinois J. Surg. Oncol., 23: 73-76 (June) 1983 The charts of 329 patients with metastatic cancer from an undetermined primary site were reviewed. Adenocarcinoma followed by squamous cell carcinoma has been the most frequent diagnosis. Lymph nodes are the most common metastatic sites. In this series, as well as in other reviews, it appears that the larger the size of the metastases the poorer the prognosis. Also, patients with pulmonary metastases do worse than those with metastases to other sites. These authors advocate an early comprehensive therapy of such patients. 1 figure, 5 tables, 8 references

Abstracter's comment. Our experience with carcinoma of an undetermined site has been rewarding in that we have special stains for prostatic, bladder and testicular cancer. In the older age group carcinoma of the prostate should be considered and immunoperoxidase studies on metastatic tumor usually show acid phosphatase and/ or prostatic tumor specific antigen. Also, in the younger age group testicular cancer should be ruled out with a-fetoproteins and/or human chorionic gonadotropin stains. Furthermore, bladder cancer may be diagnosed with application of T antigen. A renal computerized tomogram and/ or arteriogram may rule out renal cancer. These authors apparently have not applied immunocytochemical techniques in these cases. We recommend the application of these specific stains, since in our hands they have been extremely rewarding. N. J. Methadone and Intravenous Morphine Requirements. Treatment of Pain due to Advanced Cancer

E. R. KEPES, S. RAJ, P. THOMAS AND K. VEMULAPALLI, Department of Anesthesiology, Montefiore Medical Center, Albert Einstein College of Medicine, The Bronx, New York N. Y. State J. Med., 83: 925-927 (June) 1983 Pain from advanced cancer is difficult to control at times and usually is associated with anxiety and depression. The authors have studied 19 patients with advanced cancer and pain, and have reported good results with oral methadone because of a rather prolonged half-life of 4 to 6 hours. Therefore, it is not necessary for patients to be disturbed during sleep. Also, the authors have used an infusion pump for continuous morphine administration by the intravenous route. The dosage