ELECTROPHORETIC COMPARISONS OF FLUIDS FROM FOUR DIFFERENT ASCITES TUMORS AND SERA OF MICE BEARING THE TUMORS IN THE ASCITES AND SOLID FORMS.
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The local intra-osseous injection of double zinc beryllium silicate into the tibial or femoral epiphysis of a rabbit causes an osteogenic sarcoma in 70 p. 100 of cases. These experimental conditions make it possible to reveal early non specific radiological alterations, later on secondary alterations corresponding to the development of the sarcoma and finally to follow the spontaneous evolution of the tumor. Moreover, this experimental process of induction of an osteogenic sarcoma by means of a local intra-osseous injection is vastly better than an intra-venous injection which causes straight-away multiple visceral lesions.
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Jaw bones differ embryologically from limb bones and the axial skeleton as they are derived from migrating neural crest cells and are not preformed in cartilage as are the latter bone types. The purpose of the present study was to determine whether this embryologically different nature implied a different response to a locally applied carcinogenic compound, 4-hydroxyamino-quinoline-1-oxide; this within the context of elucidating why human jaw osteo- and fibrosarcomas behave differently from identical tumours elsewhere in the skeleton. Rat mandibles were exposed to the carcinogen. Of the 5 rats used, 3 developed tumours which were however histologically identical to the tumours experimentally induced in the limb bones by the same carcinogenic agent. As a consequence, it is concluded that the embryologically different nature of the jaw bone does not imply that local exposure to a carcinogenic agent induces other kinds of tumours as are seen in the extragnathic skeleton.
The histology and ultrastructure of primary central nervous system and metastatic (epidural) reticulum cell sarcoma is described. The tumors showed varying numbers of argyrophilic microglial cells which in all cases constituted a minority of all tumor cells. A primitive, undifferentiated cell, common to all tumors, was a small cell with a large dense nucleus and a narrow rim of poorly structured cytoplasm. These cells frequently showed small fatty inclusions and were tentatively identified as primitive multipotential cells from which all other tumor cells develop. It is concluded that reticulum cell sarcoma of the nervous system (primary or metastatic) and microglioma or microgliomatosis are one and the same tumor.
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The utility of combining the vascular targeting agents 5,6-dimethyl-xanthenone-4 acetic acid (DMXAA) and combretastatin A-4 disodium phosphate (CA4DP) with the anticancer drugs cisplatin and cyclophosphamide (CP) was evaluated in experimental rodent (KHT sarcoma), human breast (SKBR3) and ovarian (OW-1) tumor models. Doses of the vascular targeting agents that led to rapid vascular shutdown and subsequent extensive central tumor necrosis were identified. Histologic evaluation showed morphologic damage of tumor cells within a few hours after treatment, followed by extensive hemorrhagic necrosis and dose-dependent neoplastic cell death as a result of prolonged ischemia. Whereas these effects were induced by a range of CA4DP doses (10-150 mg/kg), the dose response to DMXAA was extremely steep; doses < or = 15 mg/kg were ineffective and doses > or = 20 mg/kg were toxic. DMXAA also enhanced the tumor cell killing of cisplatin, but doses > 15 mg/kg were required. In contrast, CA4DP increased cisplatin-induced tumor cell killing at all doses studied. This enhancement of cisplatin efficacy was dependent on the sequence and interval between the agents. The greatest effects were achieved when the vascular targeting agents were administered 1-3 hr after cisplatin. When CA4DP (100 mg/kg) or DMXAA (17.5 mg/kg) were administered 1 hr after a range of doses of cisplatin or CP, the tumor cell kill was 10-500-fold greater than that seen with chemotherapy alone. In addition, the inclusion of the antivascular agents did not increase bone marrow stem cell toxicity associated with these anticancer drugs, thus giving rise to a therapeutic gain.
Tumor chemosensitivity assays require the frequent in vitro use of antineoplastic drugs. Economy and convenience are greatly enhanced if these drugs are stored in aliquots for use as needed. This study investigated the stability of eight common antineoplastic agents at -60 degrees C. Activity was measured as inhibition of colony formation in a commonly used soft agar culture system using an experimentally induced murine sarcoma. Our results indicate no loss of activity with these drugs under the specified storage conditions.
The sarcomas are an extremely heterogeneous group of neoplasms that continue to present substantial diagnostic and therapeutic challenges. It is notable, therefore, that great strides have been made in the genetic characterization of sarcomas over the past few years. The very consistent chromosome translocations in Ewing's sarcoma, myxoid liposarcoma, and alveolar rhabdomyosarcoma have been cloned, and the oncogenes deregulated by these translocations have been identified. These characteristic genetic aberrations can now be used as diagnostic markers.
Many sarcomas contain characteristic chromosome translocations that result in the fusion of genes from two different chromosomes. This review focuses on the translocated genes that have been identified recently in Ewing's sarcoma, peripheral primitive neuroectodermal tumor, clear cell sarcoma, alveolar rhabdomyosarcoma, and myxoid liposarcoma. Each of these fusion genes encodes a DNA transcription factor that presumably regulates the function of other genes. Thus, a common mechanism of oncogenesis has been defined in histologically disparate varieties of sarcoma.
The aim of the present study was to investigate any sensitization effect of the Panax notoginseng extract (PNE) and the purified Saponin (Rb1) on the radiation response of an experimental tumor (KHT sarcoma) in mice, in comparison with any effects on a normal tissue (bone marrow). PNE at a concentration of 0.1-100 mg/kg produced an increase in tumor radiosensitivity. The sensitization effect was maximal at 10 mg/kg and at 30 minutes after injection. Higher doses were toxic to the bone marrow stem cells. Similarly Rb1 at a concentration 0.001 to 1 mg/kg also produced an increase in tumor radiosensitivity, with maximum effect at 1 mg/kg. Higher doses were not toxic to the bone marrow stem cells in this case. Radiosensitization factors were calculated as ratios of D0 (the radiosensitivity parameter), and these were highly significant for the tumor and very similar for both compounds at the doses used, namely 1.18-1.19. There was no significant effect for bone marrow stem cells (sensitization factors of 0.99 +/- 0.01 for both compounds). The differential effect on tumor, and the magnitude of the radiosensitization, suggest that further purified or synthetic versions of this extract may be useful not only in vascular-related diseases but also in cancer therapy.
BALB/c and C57 B1/6 mice which received weekly subcutaneous injections of a cannabinoid developed tumors at the points of injection. In the groin the tumors were fibrosarcomas, while in the interscapular region they were anaplastic sarcomas and synovial sarcomas. The latter developed faster and were larger in cannabinol - and cannabidiol-treated C57 B1/6 mice than in delta 9-tetrahydrocannabinol-treated BALB/c mice. This difference could not be attributed to strain differences. 2 cannabidiol- and 1 cannabinol-treated C57 B1/6 females with the fastest growing synovial sarcomas were pregnant and, in addition, 2 of them developed mammary adenocarcinomas, indicating that they were rich in estrogen. On the other hand, it is known that delta 9-tetrahydrocannabinol causes a decrease in the sex hormone. It is consequently thought that the cannabinoids are only initiators of synovial sarcoma, while growth or promotion of the latter is influenced partially or entirely by the sex hormone.
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