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[Role of growth factors in the autonomous growth of tumor cells].

Typical characteristic of tumor cells is a decreased dependence on the growth factors for promotion of their growth. Growth factor independence and autonomous growth of tumor cells has been thought to be due to the ability of the cells to produce growth factors. According to an autocrine hypothesis, growth factor can be secreted by tumor cells and then binds to its receptor on the same cells to create an uncontrolled growth stimulation. Although there has been much circumstantial evidence to support this hypothesis, an autocrine mechanism is still uncertain. We purified DSF (DNA synthesis factor) from an extract of rat Rhodamine fibrosarcoma. This factor with strong affinity for heparin-Sepharose was a basic protein with molecular weight of 17,000. These properties were similar to those of basic FGF (fibroblast growth factor). We found that primary cells from the sarcoma could grow in serum-free medium supplemented with the extract of the same sarcoma tissue. The extract was fractionated to purify proteins which supported the growth of primary cells. DSF, transferrin and albumin which localized in the tissue, not due to contamination of blood, were purified. When they were added to the serum-free medium, the cells grew at a similar rate to that in medium supplemented with serum. This finding suggests that the growth of sarcoma cells is stimulated by their own growth factor and by some environmental factors.

Animals↗

Immunohistochemistry of soft tissue tumors: progress and prospects.

The immunohistochemical definition of soft tissue tumors has only begun (table 1). A number of antigens described here play a role in diagnostic pathology, and a few have been shown to be specific markers for certain types of cell differentiation. The detection of a wide variety of antigens in soft tissue sarcomas may initially prove confusing in some areas. For example, when specific markers are used, multidirectional differentiation in a tumor may be found more frequently than it is now, making more sarcomas actually "mesenchymomas." In such situations, certain types of differentiation may imply more or less aggressive behavior. It is also possible that panels of different immunohistochemical reagents may be required to determine a specific histogenesis. Furthermore, interpretive caution is clearly necessary, since many sarcomas contain normal tissues. Owing to the aggressive nature of sarcomas, more information on their biochemical composition will be required for proper diagnosis and clinical management. As pathologists, we are in a key position to contribute to the understanding of these tumors. In-situ biochemical analysis of sarcomas making use of immunohistochemical methodology is a powerful tool in the investigation of the difficult problems of histogenesis, tumor heterogeneity, and biologic potential.

Antigens, Neoplasm↗

Characterization of intra-tumoral porphyrin following injection of hematoporphyrin derivative or its purified component.

Photodynamic therapy (PDT) utilizes either hematoporphyrin derivative (Hpd) or a purified form of Hpd termed DHE, as photosensitizers for treatment of a variety of solid tumors in man. The reasons for long retention of these porphyrins in a wide range of histologically diverse tumors remain obscure. We have found that the RIF fibrosarcoma and SMT-F mammary carcinoma in mice, a intrapancreatic tumor in the hamster and a tumor removed from a patient with a myxoid sarcoma, make take up Hpd or DHE by endocytosis. On the other hand the RIF tumor cells in vitro show a tendency for selective uptake and retention of the more hydrophobic components of the mixture.

Animals↗

Histological changes in the submandibular glands of rats after intraductal injection of chemical carcinogens.

Carcinogens injected into the excretory canal of submandibular gland of Donryu rats revealed the following histologic changes in salivary glands. 20-Methylcholanthrene induced squamous cell metaplasia, fibrosis in the early stages, and "benign lymphoepithelial lesion"-like pattern after 3 months. Dense hyalinization occurred after 4-5 months with so-called "mixed tumor"-like pattern. In the later stages epidermoid carcinoma and fibrosarcoma were observed. 9, 10-Dimethylbenzanthracene caused degenerative change, metaplasia, fibrosis and cell infiltration, and later carcinoma and sarcoma appeared at a high rate. 4-Nitroquinoline-N-oxide led to dense hyalinization and so-called "mixed tumor"-like pattern was observed in many specimens. N-nitroso-N-methyl urethane and N-methyl-N-nitroso-N'-nitroguanidine revealed metaplastic changes, fibrosis and lymphoid infiltration. Scarlet red induced remarkable infiltration and aggregation of lymphoid cells, showing benign "lymphoepithelial lesion"-like pattern.

4-Nitroquinoline-1-oxide↗

Biological and biochemical characterization of a new isolate of feline sarcoma virus: Theilen-Pedersen (TP1-FeSV).

A new feline sarcoma virus designated Theilen-Pedersen (TP1-FeSV) has been isolated from a spontaneous, slowly growing fibrosarcoma of a domestic short-haired 4-year-old castrated cat. The virus codes for a gag-onc fusion protein of 83,000 molecular weight phosphorylated in vivo at serine, threonine, and tyrosine residues. Cells transformed in vitro with TP1-FeSV exhibit five- to 10-fold elevated levels of phosphotyrosine over FeLV-infected cells. The gag-onc polyprotein has associated with it a tyrosyl protein kinase activity which in vitro results in autophosphorylation of the molecule at tyrosine residues. The fusion protein cannot be labeled metabolically with [3H]glucosamine and tunicamycin has no effect on the electrophoretic mobility of the in vivo [32P]orthophosphate-labeled fusion protein. The fusion protein, in common with the gag precursor Pr65gag, can be metabolically labeled with palmitic acid.

Acylation↗

Reactive glioma in intracranial sarcoma: a form of mixed sarcoma and glioma ("sarcoglioma"): report of eight cases.

The clinicopathologic features of eight new cases of combined intracranial sarcoma and glioma are described. This type of mixed cerebral tumor is histologically characterized by a peripheral distribution of the gliomatous elements in relation to a more centrally situated meningeal or intracerebral sarcoma, and by the frequent presence of gradual transitions from reactive to frankly neoplastic astrocytes. In six of the eight cases, the additional development of either infiltrating astrocytoma or frank glioblastoma in the adjacent brain was demonstrated; this was interpreted as a further expression of malignant glial reaction. It is suggested that these tumors be termed "sarcogliomas" to distinguish them from the type of mixed glioma and sarcoma that has recently been redesignated "gliosarcoma."

Adolescent↗

Retroperitoneal sarcomas: a reappraisal of treatment.

Retroperitoneal sarcoma, regardless of the histopathologic grade of malignancy, has a high incidence of local recurrence that is usually fatal. Surgical resection is mandatory and resectability may be improved by a midline transabdominal approach. However, even with total tumor excision, recurrence is high. A preliminary study, combining resection and preoperative adriamycin, found to be effective for established disease, suggests potentially improved prognosis. Further clinical trials employing combined with adjuvant chemotherapy are warranted.

Adolescent↗

Biological activities of dihydrodiols derived from two polycyclic hydrocarbons in rodent test systems.

Comparisons have been made between (a) the initiation of tumours in mouse skin, (b) the induction of hyperplasia and the suppression of sebaceous glands in mouse skin and (c) the induction of s.c. tumours in rats, by either benzo[a]pyrene or 7-methylbenz[a]anthracene and their related K-region and non-K-region dihydrodiols. Whilst the 3,4-dihydrodiol derived from 7-methylbenz[a]anthracene is more active than the hydrocarbon in initiating tumours in mouse skin (subsequently promoted by a phorbol ester) the 7,8-dihydrodiol of benzo[a]pyrene is very much less active than benzo[a]pyrene itself in the induction of hyperplasia or the suppression of sebaceous glands in mouse skin or in the induction of s.c. sarcomas in rats. Since much other evidence suggests that the 3,4-dihydrodiol of 7-methylbenz[a]anthracene and the 7,8-dihydrodiol of benzo[a]pyrene are the dihydrodiols involved, via the related vicinal diol-epoxides, in the metabolic activation of these hydrocarbons, mouse skin initiation-promotion experiments may be more useful for the identification of such diols than the other two in vivo tests for biological activity used here.

Animals↗

R7, a spontaneous mutant of Moloney murine sarcoma virus 124 with three direct repeats and an in-frame truncated gag-mos gene, induces brain lesions.

We have isolated Recombinant 7 (R7), a spontaneous mutant of SV7, a molecular clone of MoMuSV124. Like SV7, R7 induces subcutaneous fibrosarcomas, spleen tumors, and mesentery tumors infiltrated by proliferating vessels lined by transformed endothelial cells. However, it also induces brain lesions. We have molecularly cloned and sequenced the R7 proviral DNA and shown that the R7 genome consists of 3401 bp. It has three direct repeats in each enhancer. Its coding sequence consists of only 176 bp of p15, 263 bp of p30, a 7-bp insertion, and 853 bp of an N-terminally truncated mos gene. From the sequence of R7 we have deduced that the truncated mos sequence is in-frame with all of the gag sequence and the 7-bp insertion. The incorporation of the 3' end of the p15 sequence further suggests that the R7 Gag-Mos is myristylated. We have also shown that the molecularly cloned R7 virus transformed NIH/3T3 fibroblasts about sevenfold better than the parental SV7. We have also confirmed that molecularly cloned R7 induces the same disease phenotype as that induced by the nonmolecularly cloned R7.

Amino Acid Sequence↗

MS-2 fibrosarcoma characterization by laser induced autofluorescence.

BACKGROUND AND OBJECTIVE: MS-2 fibrosarcoma implanted in BALB-CDF1 mice was investigated by frequency and time domain measurements of the autofluorescence (AF) radiation emitted upon excitation by a N(2) laser beam (337.1 nm). STUDY DESIGN/MATERIALS AND METHODS: AF spectra were obtained by using a spectrograph, a multichannel plate and an optical multichannel analyzer for the steady state detection. Time-resolved spectra were performed by means of a monochromator, a photomultiplier, and a digital signal analyzer. RESULTS: Spectral measurements show that the autofluorescence intensity of pathologic tissue is lower than that of healthy one in the 400- to 500- spectral region. In the same spectral range, we found the fluorescence decay to be the sum of a fast and a slow component. The lifetime of the fast component of tumoral tissue is significantly lower than that of healthy samples. CONCLUSION: Frequency and time domain measurements used in combination show that MS2-fibrosarcoma is characterized by the probable presence of the free form of NADH.

Animals↗

The defined attenuated Listeria monocytogenes delta mp12 mutant is an effective oral vaccine carrier to trigger a long-lasting immune response against a mouse fibrosarcoma.

Listeria monocytogenes has been proposed as a carrier to elicit major histocompatibility complex class-I restricted immune responses able to protect against tumor challenge. In this study the properties of the attenuated L. monocytogenes delta mp12 mutant has been evaluated in vivo against a highly aggressive mouse fibrosarcoma which expresses beta-galactosidase (beta-gal) as a tumor-associated antigen (TAA). Immunization with the vaccine prototypes resulted in both elicitation of specific antibodies and generation of cytotoxic lymphocytes (CTL). Oral vaccination protected 55-64% of the immunized animals from tumor take (p < 0.01) and strongly reduced the average size of the tumor in the other 34-45% (p < 0.01). Vaccinated mice developed a long-lasting response, which resulted in 100% protection from a subsequent tumor challenge. Substitution of the whole TAA by its CTL-defined immunodominant epitope resulted in 43% protection, suggesting a contribution of the humoral response to the observed antitumor effect. No statistically significant differences were observed in the antitumor response when mice were immunized with strains expressing the immunodominant TAA epitope in the context of carrier proteins which were either exported or restricted to the bacterial cytoplasm. This suggests that the topology of the recombinant antigen does not play a major role in the outcome of the protective response.

Administration, Oral↗

The combined effect of radiotherapy and neuraminidase-treated tumor cells on 3-methylcholanthrene-induced fibrosarcoma.

Active immunotherapy with tumor cells treated in vitro with Vibrio cholerae neuraminidase (VCN) plus mitomycin C augments the antitumor effects of local x irradiation in the treatment of firmly established methylcholanthrene-induced fibrosarcoma, MC-43, in syngeneic C3H/HeJ female mice. In most experiments, the inhibition of tumor growth was greater when VCN-treated tumor cells were combined with local irradiation than could be achieved with VCN-treated tumor cells or local irradiation alone. Even in those experiments in which the immunotherapeutic effect of VCN-treated cells was negligible, the combination of radiotherapy and immunotherapy appeared to be greater than irradiation alone. Similarly, total permanent regression of established tumors occurred more frequently after combined therapy than after immunotherapy or radiation therapy alone.

Animals↗