The process of metastasis is highly selective and favors the survival and growth of a few subpopulations of cells that preexist within a heterogeneous primary neoplasm. To produce metastases, tumor cells must succeed in invasion, embolization, survival in the circulation, arrest in a distant capillary bed, and extravasation into and multiplication in organ parenchyma. The outcome of this process depends on the interaction of metastatic cells with multiple host factors. To assess metastatic potential accurately, it is necessary to orthotopically implant human tumor cells recovered from surgical specimens into nude mice. This orthotopic implantation of tumor cells is invariably associated with trauma to the specific organ of implantation, which is followed by the processes of inflammation and repair. Tissue-specific growth factors may be responsible for stimulation of tumor cells that possess specific surface receptors. Understanding the factors that regulate cancer metastasis should allow for the design of rational therapy.

Animals↗

PubMedDate not supplied

Adriamycin-ifosfamide induction chemotherapy for extremity soft tissue sarcoma: comparison of two non-randomized protocols.

Chemotherapeutic cytoreduction of soft tissue sarcomas may permit less radical operation. In cases of large or multi-compartmental masses, deeply seated tumors or involvement of a neurovascular bundle, down-sizing of the mass is required before limb sparing surgery can be considered. We have applied a combination chemotherapy consisting of intravenous adriamycin and ifosfamide with intra-arterial cisplatin for patients with soft tissue sarcomas of the extremity as induction treatment, and switched to an intravenous-only protocol due to toxicity and management difficulties. Adjuvant chemotherapy and radiation therapy were given after limb-sparing surgery in both regimens. Fresh tumor specimens were obtained and were examined for tumor size, surgical margins, percent of necrosis, evidence of vascular or perineural invasion, and the presence of Pgp, Ki-67, p53, PCNA and bcl-2-oncoprotein. Our results in terms of percentage of tumor necrosis were comparable and even better in favor of the second regimen [38% good histological response with intravenous (i.v.)-only versus 12.5% for combined i.v. + intra-arterial (i.a.]. The clinical and radiological responses were also better for the second (i.v. only) regimen (45%) than for the first (i.v. + i.a.) regimen (12.5%). The toxicity and the inconvenience to the patients and to the treating staff were greater in the first regimen that combined intra-arterial and intravenous infusions. In the first group the failure rate is 75% within 32 months of follow-up, while it is 33% within 12 months follow-up in the second group. The immunohistochemical markers did not correlate with disease control nor with the patient outcome. Intravenous administration of ADR-IFX induction chemotherapy was more feasible than combined i.v. ADR-IFX plus i.a. cisplatin and achieved better results.

Adult↗

PubMedDate not supplied

Treatment and prevention of use and abuse of illegal drugs: progress on interventions and future directions.

State-of-the-art downstream interventions are generally successful for half of drug-abusing clients. But, only one in four abusers actually receives treatment. In the midstream, one setting (schools), one type of prevention ("one size fits all"), and a limited age-range focus (adolescence and preadolescence) have predominated. Accumulating evidence casts doubt on the effectiveness of widely disseminated school-based prevention approaches, although theory-based programs that emphasize skills training and adjunctive parent and neighborhood interventions fare better. Newer pursuits include intervening very early with higher risk children and expanding to primary health care settings and workplaces. Popular but unproven community approaches need more rigorous evaluation. Upstream national and state public policy and environmental interventions should be reexamined in light of their success for preventing tobacco and alcohol use.

Health Promotion↗

PubMedDate not supplied

Accelerated growth of human colon cancer cells in nude mice undergoing liver regeneration.

The purpose of this study was to determine whether liver regeneration induced by partial hepatectomy (PH) influences the growth of human colon cancer (HCC) cells implanted into athymic nude mice. HCC KM12C cells were injected subcutaneously into nude mice and then the mice were randomized to undergo PH, laparotomy, or no surgery. The latent period to development of measurable tumors was shorter and the growth rate of HCC tumors was significantly faster in hepatectomized mice. Accelerated tumor growth directly coincided with liver regeneration. Peak mitotic activity in both the regenerating liver and HCC occurred on the second day following PH. No enhancement in growth of tumors occurred in mice implanted with HCC cells 3 weeks after PH (i.e. 2 weeks after completion of liver regeneration). The accelerated tumor growth was specific to HCC. We base this conclusion on results of control experiments where cells from human melanoma, colon, breast, prostate, and renal cancer were injected into nude mice that were then randomized to undergo PH or laparotomy. Only HCC grew faster in hepatectomized mice. No significant differences in expression of epidermal growth factor receptor (EGF-R) and c-met were found between HCC tumors in mice with PH or laparotomy, suggesting that over-expression of EGF-R or c-met is not an essential component of this phenomenon. The accelerated growth of HCC cells at a site distant from surgical trauma suggests that circulating growth factors involved in liver regeneration can specifically stimulate the growth of HCC cells.

Animals↗

PubMedDate not supplied

Intertumoral heterogeneity of receptor-tyrosine kinases expression in human melanoma cell lines with different metastatic capabilities.

Human melanocytes respond to several growth factors whose receptors have tyrosine kinase activity. Abnormalities in the expression of tyrosine kinase receptors may play an important role in the initiation and progression of melanoma. We therefore determined the steady-state mRNA expression of five tyrosine kinase receptors, epidermal growth factor receptor (EGF-R), c-met, nerve growth factor receptor (NGF-R), colony-stimulating factor receptor (CSF-R) and c-kit, in eleven human melanoma cell lines with different metastatic potentials in nude mice. All cell lines except for one nonmetastatic line established from a primary melanoma lost expression of c-kit. Expression of the other four tyrosine kinase receptors varied among the lines. The expression level of individual tyrosine kinase receptor did not correlate with the metastatic potential of the cells. These results suggest that metastatic human melanoma cell lines are heterogeneous for expression of tyrosine kinase receptors, with each cell type manifesting a distinct repertoire of receptor tyrosine kinases. The different profile of tyrosine kinase activities in different metastatic melanomas complicates its use for prognosis.

Animals↗

PubMedDate not supplied

Failure of thalidomide to inhibit tumor growth and angiogenesis in vivo.

Thalidomide was recently suggested to be angiogenesis-inhibitor following the demonstration of its activity in a rabbit cornea micropocket model. The purpose of the present study was to test its efficacy in solid tumors in mice. B16-F10 melanoma and CT-26 colon carcinoma cells were injected subcutaneously, intravenously and intraperitoneally, and mice received daily gavage of 0.3-1.0 mg thalidomide starting either two or 10 days following tumor cell injection. The tumors were measured and compared with controls. There was no growth retardation in CT-26 bearing mice nor in mice with pulmonary or peritoneal metastases of B16-F10 melanoma. In 3/7 groups of mice with SC B16-F10 tumors, growth retardation was demonstrated, however the difference was not statistically significant. All tumors eventually reached maximal size, similar to controls. Morphological evaluation of the blood vessels oriented towards the tumor revealed that in both thalidomide and control groups, all mice had developed an intact network of new blood vessels. In our model for the oral administration of thalidomide inhibition of tumor growth and angiogenesis did not occur. We hypothesize that the lack of sustained antiangiogenic response was either due to immune modulation or to tumor heterogeneity and adaptation.

Animals↗

PubMedDate not supplied

Establishment of a reproducible transplantable sarcoma in a rat.

BACKGROUND: Animal models are valuable tools in cancer research. Mice are the most commonly used animals but for surgical procedures, such as bowel anastomosis and organ perfusions, larger animals (e.g. rats) are preferable. Unfortunately, rat cell-lines are scarce and rat strains are ample, so that adaptation of a cell-line to the specific strain used in individual laboratories is difficult. In this study we present a simple and reproducible model of rat carcinogenesis. MATERIAL AND METHODS: Carcinogenesis was induced by 7,12 dimethylbenzantracene dissolved in wax and paraffin at 60 degrees C. For matrix production, we used HTR polymers. The resulting particles were implanted subcutaneously (SC). RESULTS: Tumors occurred in all rats. The resulting tumors, designated GF, were locally invasive with low metastatic potential. In vitro doubling time was 7.5 hours. Injection of 5 x 10(6) cells or transplantation of a tumor fragment resulted in a visible tumor within six weeks. The histologic picture and immunohistochemical pattern were consistent with pleomorphic soft tissue sarcoma of myogenic origin. CONCLUSIONS: This method will enable an individual laboratory to create and maintain a sarcoma cell line that will effectively grow in its own rats.

Actins↗