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At least 73 records · Page 4Linked to original sources
PubMed1992

Cancer cachexia is transmissible in plasma.

The cause of cancer cachexia is unclear. Tumors may be competing with the host for ingested nutrients or may be releasing some factor that actively inhibits energy utilization. To explore these questions, plasma was sterilely collected and pooled from 103 terminally cachectic Fischer 344 rats implanted with an experimental sarcoma. Control plasma was collected in similar fashion from 138 nontumor-bearing rats (NTBP). Plasma from tumor-bearing rats (TBP) or NTBP was continuously infused in a randomized, blinded fashion for 4 days into 20 normal rats. During infusion, food intake and nitrogen excretion were measured daily. At sacrifice, body weight and organ masses were determined. Rats receiving TBP demonstrated an immediate and profound anorexia compared with those receiving NTBP. Total food intake during treatment was 31.2 +/- 3.3 (g +/- SEM) in the TBP group versus 48.2 +/- 2.8 in the NTBP group (P less than 0.001 by t test). Likewise, the total decline in body weight was greater in the TBP group as compared with the NTBP group (-35.2 +/- 3.4 versus -14.6 +/- 4.0, P less than 0.001). Mean daily nitrogen balance during treatment was negative in the rats receiving TBP (-14.5 +/- 20.1 mg +/- SEM) while remaining highly positive in the rats receiving NTBP (110.7 +/- 19.3, P less than 0.002). Finally, cardiac and gastrocnemius muscle masses were decreased, while hepatic mass was unaffected. These data demonstrate that the syndrome of cancer-associated cachexia is transmissible in plasma and therefore may be mediated by a circulating molecule or molecules. Identification and purification of the molecule(s) responsible for this effect would have obvious clinical benefits.

Animals↗
PubMed1992

Selective depletion of tumor ATP by 2-deoxyglucose and insulin, detected by 31P magnetic resonance spectroscopy.

The purpose of this study was to investigate whether substrate deprivation acutely and selectively decreases ATP concentration in an experimental sarcoma. Two methods of substrate deprivation were examined: glycolysis was inhibited using 2-deoxyglucose (2DG), and plasma substrate levels were reduced using insulin. The effects of treatment on tumor ATP, inorganic phosphate, and pH were studied by 31P nuclear magnetic resonance spectroscopy. 2DG (2 g/kg) was administered i.p. to rats bearing s.c. methylcholanthrene-induced sarcomas. Inhibition of glycolysis by 2DG caused a 52 +/- 13% (SE) decrease in the tumor ATP to inorganic phosphate ratio, associated with a decrease in pH of 0.38 +/- 0.10 unit. The same dose of 2DG caused no significant change in the ratio of phosphocreatine to ATP in brain. Insulin (125 units/kg, i.p.) caused a 68% decline in plasma glucose and a 71% decline in betahydroxybutyrate compared to saline-treated animals. Concomitantly, 31P nuclear magnetic resonance spectroscopy detected a 48 +/- 13% decrease in sarcoma ATP, with a reciprocal elevation of inorganic phosphate in insulin-treated animals. In contrast, the brain phosphocratine/ATP ratio was unaffected by insulin. These results suggest that large tumors are acutely sensitive to inhibition of glycolysis and reductions in plasma levels of substrates for oxidative phosphorylation and glycolysis, while the brain is unaffected. In addition, this work provides support for the use of 31P nuclear magnetic resonance spectroscopy to monitor tumor response to therapy.

Adenosine Triphosphate↗
PubMed1989

Characterization of the pseudocapsule of soft-tissue sarcomas. An experimental study in rats.

The effect of preoperative radiation therapy on the pseudocapsule of experimental rat soft-tissue sarcomas has not been histologically evaluated in a controlled study. The irradiated animal showed marked thickening of the capsular structure surrounding the sarcoma. Everywhere morphologically distinct from the tumor, there was no evidence of tumor invasion into or through this capsular structure. The membrane was consistently thicker and more hyalinized than in the control animals. The nonirradiated animals showed a minimal pseudocapsular structure with a characteristic tumor penetration. Irradiation produced distinct histologic changes in the pseudocapsule. Although assumed on the basis of clinical observations alone, irradiation-induced pseudocapsule has not previously been demonstrated in an experimental model of soft-tissue sarcoma.

Animals↗
PubMedDate not supplied

Presarcomatous lesions of experimentally induced sarcomas in rats: morphologic, histochemical, and immunohistochemical features.

Morphological studies have been performed mainly on manifest sarcomas, leading to divergent views of its histogenesis. However, histogenesis requires understanding of the tumor precursor cells and cannot be resolved by static morphologic studies. Defining presarcomatous lesions is made more difficult because they do not possess a basement membrane that serves as biologic and nosologic boundary like in epithelial cancers. The present study, therefore, investigated the early phases of experimentally induced rat sarcoma, which closely resembles human malignant fibrous histiocytoma (MFH). Histological, enzyme- and immunohistochemical methods were used to define the sequential events involved in tumorigenesis. A benzo[a]pyrene-oil mixture was injected intramuscularly into the thighs of rats, producing MFH 120 days later. Groups of animals were sacrificed every 10 days. The injections produced soft tissue lesions characterized by three distinct phases that overlapped or existed simultaneously in one animal: an initial acute inflammatory reaction characterized by an infiltration of lymphocytes, monocytes and macrophages, a second mesenchymal fibromatous phase characterized by the predominance of spindle-shaped, focally atypical fibroblast-like cells and collagen, and a third premalignant neovascularization phase characterized by dominant capillary proliferations. Overt MFH developed 120 days after injection and consisted of spindle-shaped fibroblast- and histiocyte-like cells containing atypical mitoses and arranged in a storiform pattern. Control animals injected with olive oil revealed acute inflammatory reactions after 30 days and no signs of chronic inflammation or malignancy after 60 and 120 days. We concluded that these experimentally-induced rat sarcomas develop in a triphasic pattern that resembles non-healing granulation tissue, with neovascularization preceding the occurrence of overt MFH.

Animals↗
PubMed2001

Effect of modified tumor antigen on experimentally induced sarcomas.

OBJECTIVE: To explore the possibility of controlling established tumors by active immunization through specific and nonspecific methods. METHODS: By subcutaneous methylcholanthrene, a fibrosarcoma was produced in adult Swiss male mice. The fibrosarcoma was transplanted into the isogenic strain. The cleared tumor cells were injected subcutaneous into the hind leg of the 1st sarcoma group. The 2nd group received intraperitoneally sensitized spleen cells. One section of the irradiated 3rd tumor group received intraperitoneally sensitized spleen cells and subsequently a mild dose of modified tumor antigen. The 2nd section of the 3rd group was irradiated in between the administration of modified tumor antigen. In both the groups, liver of normal and transplanted tumor bearing mice was processed and intraperitoneally injected into the isogenic tumor bearing mice. Histopathology and tumor size by calipers was assessed. RESULTS: The first group showed enhancement of tumor growth in all its 3 fractions injected at different intervals. In the 2nd group, the average survival period was prolonged. In the first section of the 3rd group a decrease in tumor size and protracted survival was noted. In the transplanted tumor bearing mice, complete suppression of tumor growth was observed. In the 2nd fraction of the 3rd group, long survival period with regression of tumor was observed. In the 4th group, attenuated tumor and one mouse was observed to become tumor free after 60 days. CONCLUSION: Active immunosuppression by sensitized spleen cells and vaccines from transplanted sarcomas enabled regression of tumor size and longevity in tumor bearing mice. The modified tumor antigens, processed isogenic liver cells attenuated to zero level in tumor size in isogenic transplanted tumor bearing mice. The results show vaccines from allogenic and syngeneic sources bear the potential to regress tumor and enhance survival period.

Animals↗
PubMed1988

In adequate tumor surgery of chemically induced soft tissue sarcomas--an experimental approach for induction of metastasis formation?

In preceding experiments with nude mice bearing xenotransplanted soft tissue sarcomas after inoculation of cultured sarcoma cells we attained a high percentage of metastatic dissemination by repeated inadequate tumor surgery. In the study presented here we used methylcholanthrene induced sarcomas (rhabdomyosarcomas and undifferentiated sarcomas in part showing the picture of storiform/pleomorphic malignant fibrous histiocytomas) which were produced in NMRI mice and examined (1) whether or not metastasis formation could be triggered or enhanced by repeated inadequate tumor surgery in these animals, and (2) the efficacy of the same surgical procedure following xenotransplantation of the tumors into nude mice. We did not reach an increasing frequency with both experimental arrangements. After discussing several factors which could be in general responsible for inducing metastasis formation and after comparing the results of our several experiments it is suggested that the methylcholanthrene induced soft tissue tumors may not contain cell clones able to metastasize.

Animals↗
PubMed1983

Experimental-induced sarcomas after intra-articular injection of 9-10-dimethyl-1-2-benzanthracene.

The authors describe an experimental study on rabbits whereby the development of sarcomas was induced following injection into the knee joint with 9-10-dimethyl-1-2-benzanthracene. The results of the experiment are in contrast to those of other authors as no "synovialoma" or synovial sarcoma developed but only morphological patterns which might belong to malignant fibrous histiocytoma and occasionally fibrosarcoma. In accord with our results the hypothesis is discussed that all malignant mesenchymal neoplasias result from a not clearly identifiable pluripotent mesenchymal stem cell.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Cytogenetics and experimental models of sarcomas.

Bone and soft tissue sarcomas are diagnostically challenging. Recognition of specific cytogenetic abnormalities in these neoplasms has significantly reduced some of the associated difficulties and has provided valuable information on histopathogenesis. Commonly, translocations involving an exchange of chromosomal material and creation of novel chimeric genes are detected. These fusion genes frequently function as aberrant transcription factors that contribute to sarcomagenesis. New studies indicate that less commonly occurring variant fusion genes are also present in some tumors, eg, Ewing's sarcoma and alveolar rhabdomyosarcoma. The clinical consequences, if any, of these variant hybrids are not yet known. Reverse transcriptase polymerase chain reaction and are useful approaches in detecting these transcripts. In addition to translocations, supernumerary ring chromosomes are often encountered in sarcomas, particularly those of intermediate or borderline malignancy. Traditional fluorescence in situ hybridization, and recently, comparative genomic hybridization have uncovered the chromosomal composition of these rings as well as some associated gene amplifications in well-differentiated liposarcoma and dermatofibrosarcoma protuberans.

Animals↗