The experimental treatment of a rat sarcoma (McFiFi 2) by intratumoral injection of BCG2 is described. Tumors which have a mean diameter of less than 10 mm at the beginning of treatment are fully susceptible to BCG, although spontaneous regression is not observed at this stage. The effective dose of living BCG ranges from two injections of 0.1 mg to two injections of 1 mg, given IT at an interval of 7 days. The permanent cure of a proporation of the tumors may also be induced by IT injection of a similar dose of heat-killed BCG or of MER, or of 10(9) heat-killed C. parvum, according to the same schedule. Preimmunization of the rats with living BCG does not improve the efficiency of heat-killed BCG. Direct contact between the therapeutic material and the tumor cells is critical. If rats are grafted with two pieces of the same tumor in widely separated sites, the intratumoral treatment of only one of these tumors with living BCG is sufficient to induce regression of both tumors in 50% of the animals. The effect of BCG is counteracted by injection of silica or by ingestion of polaramine. The same intratumoral treatment with living BCG was applied to different rat and mouse tumors. Only McFiFi 2 tumors were cured by intralesional BCG. C3H mouse plasmocytoma 5563 was not cured by intratumoral BCG but its growth could be prevented by mixing BCG and tumor cells at the time of grafting; this tumor was considered to be of medium susceptibility. However, until there is definite proof that the two mechanisms are identical, one should consider the regression and cure of a growing tumor, and the prevention of tumor growth, as two different phenomena. The clinical treatment of human tumors resembles the first experimental procedure more closely than the second.
ULTRASTRUCTURAL ASPECTS OF MOUSE TUMORS INDUCED BY ADENOVTRUS 12In a study of the ultrastructure of tumors induced in mice by adenovirus 12, no intranuclear adenovirus particles could be found. In some nuclei, however, there were inclusions resembling those observed during the lytic cycles of adenovirus 12. There was an abundance of intracytoplasmic particles of type A and type C. Deposits of a very dense substance were found along the external surface of the cell membranes and also in the neighborhood of the Cparticles.
Small-Cell Lung Carcinoma: A Systemic DiseaseStudies of small-cell lung cancer (SCLC) have accumulated a vast amount of data over the past few years; but despite these efforts almost no therapeutic progress has been made during that period. Increased usage of chemotherapy, with or without radiotherapy (Morstyn et al., 1984), has not produced signijicant improvements in results.One problem in putting together the numerous pieces of this puule is that there is no available experimental model. We can only rely on a collection of human clinical or biological observations. Until recently, these observations have been interpreted to support a cellular hypothesis for the etiology of the disease. Now, an alternative hypothesis is being developed utilizing the same established facts to implicate the neuroendocrine system. This conceptual reorganization of information is providing new insights into the disease and leading to new proposals for treatment.The cellular hypothesis can be described as a linear sequence of phenomena. Initially, one or several toxic agents induce genomic alterations in bronchial cells. Translocations or deletions of chromosomes in the regions containing cellular oncogenes may play an important role in the development of neoplasia. Gene activation results in the secretion of ectopic hormones including calcitonin, ACTH, ADH and bombesin (Hansen et aI., 1980). SCLC lines appear to produce factors that simulate their own growth during cloning and the multiplication of other SCLC lines. One such factor, which is a putative autocrine stimulus, has been identijied as bombesin (Carney et al., 1983).Screening for new active drugs, developing molecular probes to detect drug or radiation resistance, identibing growth factors and inhibitors to modilS) SCLC growth in vivo, and using antibodies directed against tumor cell surface antigens or against stimulating growth factors, growth factors' antagonists, and growth factors' receptor antagonists are the hopejid avenues of therapeutic progress in SCLC based upon the cellular hypothesis.The cell of origin for SCLC has not been identijied, but it has neuroendocrine phenotypic characteristics that do not necessarily reflect origin from an endocrine progenitor cell, but rather a development resulting from a particular route of differentiation (Gould et al., 1983). SCLCs belong to a spectrum of endocrine neoplasms originating in non-neoplastic and preneoplastic structural derangements: hypelplasias and neoplasias (Gould et al., 1978; Paladugu et al., 1985).The neuroendocrine, or systemic, hypothesis is supported by a number of research jindings. Abnormally elevated serum levels of immunologically determined peptide hormones are found in up to 70% of patients with SCLC. On the other hand, a rather low incidence (about 5 % ) of paraneoplastic syndromes is reported in these patients. This discrepancy has led to speculation that these peptide hormones are biologically inactive (Havermann et al., 1985). Biochemical analysis supports this theory since the tumor cells secr...
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