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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microspheres conjugated to radioisotopes and chemotherapeutic agents are playing an important investigative and clinical role in the management of metastatic neoplasms. The purpose of our investigation was to histologically assess the basis for regional intra-arterial microsphere therapy, by comparing the spatial distribution of microspheres in the tumor and liver of experimental models of hepatic metastases. Three New Zealand white rabbits with hepatic VX2 tumor implants were arterially injected with hepatic doses of either 15 or 30 million blue-dyed, polystyrene microspheres (27 microns-diameter). Microscopic examination of random liver and tumor samples revealed that 6-12 times as many microspheres were embolized within tumor than in normal liver (p less than 0.002). The majority of microspheres aggregated into clusters of various size within liver and tumor vasculature, though analysis of cluster sizes illustrated an exponentially skewed distribution toward isolated microspheres. Approximately eight times as many clusters were observed in tumor than in liver (p less than 0.008). Finally, a morphometric analysis was used to quantitate the minimal distances separating microsphere clusters, the intercluster distance (ICD). Analysis of over three thousand intercluster measurements revealed a median ICD approximately five times lower in tumor than in liver (p less than 1 x 10(-8)). This microquantitative analysis provides a fundamental description of how regional intra-arterial microsphere therapy allows the targeted delivery of microspheres to neoplastic tissue, to potentially improve the therapeutic index in the treatment of hepatic metastases.
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PMID:Microscopic analysis of arterial microsphere distribution in rabbit liver and hepatic VX2 tumor. 175 28

The efficacy in cancer treatment of novel therapeutic agents such as monoclonal antibodies, cytokines and effector cells has been limited by their inability to reach their target in vivo in adequate quantities. Molecular and cellular biology of neoplastic cells alone has failed to explain the nonuniform uptake of these agents. This is not surprising since a solid tumor in vivo is not just a collection of cancer cells. In fact, it consists of two extracellular compartments: vascular and interstitial. Since no blood-borne molecule or cell can reach cancer cells without passing through these compartments, the vascular and interstitial physiology of tumors has received considerable attention in recent years. Three physiological factors responsible for the poor localization of macromolecules in tumors have been identified: (i) heterogeneous blood supply, (ii) elevated interstitial pressure, and (iii) large transport distances in the interstitium. The first factor limits the delivery of blood-borne agents to well-perfused regions of a tumor; the second factor reduces extravasation of fluid and macromolecules in the high interstitial pressure regions and also leads to an experimentally verifiable, radially outward convection in the tumor periphery which opposes the inward diffusion; and the third factor increases the time required for slowly moving macromolecules to reach distal regions of a tumor. Binding of the molecule to an antigen further lowers the effective diffusion rate by reducing the amount of mobile molecule. Although the effector cells are capable of active migration, peculiarities of the tumor vasculature and interstitium may be also responsible for poor delivery of lymphokine activated killer cells and tumor infiltrating lymphocytes in solid tumors. Due to micro- and macroscopic heterogeneities in tumors, the relative magnitude of each of these physiological barriers would vary from one location to another and from one day to the next in the same tumor, and from one tumor to another. If the genetically engineered macromolecules and effector cells, as well as low molecular weight cytotoxic agents, are to fulfill their clinical promise, strategies must be developed to overcome or exploit these barriers. Some of these strategies are discussed, and situations wherein these barriers may not be a problem are outlined. Finally, some therapies where the tumor vasculature or the interstitium may be a target are pointed out.
Cancer Metastasis Rev 1990 Nov
PMID:Vascular and interstitial barriers to delivery of therapeutic agents in tumors. 229 38

In selective internal radiation (SIR) therapy of hepatic metastases, tumor vasculature is preferentially embolized with high-energy beta-emitting yttrium-90-labeled microspheres. To enable accurate estimation of the resultant absorbed radiation doses to tissues, an intraoperative beta detection probe is used to scan the liver surface. The validity of the response of this probe to Y-90 and its clinical application were assessed with a phantom containing varying activities and with biopsy samples obtained from patients being treated with SIR therapy. A linear relationship was found between the probe counts taken from the biopsy samples and the calculated tissue radiation doses from the specific activities of each sample. This relationship was repeated with probe counts determined against a water phantom containing various activities of Y-90. The probe was shown to respond minimally to bremsstrahlung. The use of the probe in measuring tissue radiation doses at laparotomy provides the opportunity to control dose administration during SIR therapy. In this way, subtherapeutic exposure of normal tissue can be assured while tumor tissue receives maximal radiation levels.
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PMID:Selective internal radiation therapy: validation of intraoperative dosimetry. 231 90

Complementary antitumor treatments are required to increase the cure rate achieved by surgery and/or radiotherapy by avoiding future recurrences and metastases. The growth of most solid tumors, particularly carcinomas, depends upon the simultaneous development of internal tumor vasculature to allow the proliferation of tumor cells. Inhibition of tumor vascularization is an indirect means of limiting tumor expansion. Daily administration of cortisone and maltose tetrapalmitate (MTP) abolished growth of implanted syngeneic C3HBA mammary tumor. Gross and macroscopic examination of these tumors revealed that tumor growth was prevented. Histological examination demonstrated lack of vascularization within the neoplastic tissue. We believe that this combination in an appropriate form could provide a prophylactic treatment regimen after conventional antitumor treatments in humans.
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PMID:Prophylactic antiangiogenic tumor treatment. 247 30

Courses of irradiation consisting of 6000 rad in ten equal fractions over 12 days delivered to KHT sarcomas in mice controlled 55% of the local tumors but 83% of the mice died from metastases. Three strategies to reduce the risk of metastatic spread were tested. The fractionation scheme was changed to deliver the same total dose using a large initial fraction followed by seven equal portions with the same overall time. ICRF-159 was used with the intention of partially synchronizing the tumor growth fraction in a radiosensitive state of the growth cycle and of promoting normalization of the tumor vasculature. Levamisole was used to stimulate the immune system. The combination of ICRF-159 with the eight-fraction radiation course proved to be effective for both increasing local control and decreasing the incidence of metastases. The addition of levamisole did not improve the results obtained with a combination of ICRF-159 and irradiation.
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PMID:The influence of ICRF-159 and levamisole on the incidence of metastases following local irradiation of a solid tumor. 729 76

Histologic cell type, largest tumor diameter and tumor location have traditionally been regarded as the leading predictors of survival for uveal melanoma. Morphological cell typing is, however, subjective to variations in interpretation. More objective classification parameters have emerged from extensive cytomorphometrical and DNA flow cytometrical studies. For patients with uveal melanoma there is no effective therapy if metastases have developed, and the median survival after clinical diagnosis of hepatic metastases is extremely poor. Current research focuses on the mechanisms underlying the metastatic process, including tumor vasculature, cytogenetics, oncogene activation, immunology, melanoma-associated antigens and tumor cell migration (cell-cell and cell-matrix interaction). Several new prognostic parameters have emerged from these studies, such as closed vascular patterns, loss of one chromosome 3, and different indices of cell proliferation. Furthermore, considerable genotypical and phenotypical differences have been found between uveal and cutaneous melanoma. In prospective studies on large series of melanomas a combination of histopathological and/or clinical prognostic parameters might be selected with high sensitivity and specificity, providing a way of selecting patients at high risk of developing metastatic disease, who might be eligible for adjuvant therapy.
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PMID:Prognostic parameters in uveal melanoma: a review. 897 Feb 36

Administration of tumor necrosis factor (TNF) and gamma interferon (IFN-gamma) to melanoma patients causes selective disruption of the tumor vasculature but the mechanism of this disruption is unknown. Here we report that exposure of human endothelial cells to TNF and IFN-gamma results in a reduced activation of integrin alphaVbeta3, an adhesion receptor that plays a key role in tumor angiogenesis, leading to a decreased alphaVbeta3-dependent endothelial cell adhesion and survival. Detachment and apoptosis of angiogenic endothelial cells was demonstrated in vivo in melanoma metastases of patients treated with TNF and IFN-gamma. These results implicate integrin alphaVbeta3 in the anti-vascular activity of TNF and IFN-gamma and demonstrate a new mechanism by which cytokines control cell adhesion.
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PMID:Evidence for the involvement of endothelial cell integrin alphaVbeta3 in the disruption of the tumor vasculature induced by TNF and IFN-gamma. 954 82

The significance of neoangiogenesis in the metastasis of nasopharyngeal carcinoma (NPC) was investigated to clarify the role neovascularity in the prognosis of NPC and the probability of antiangiogenesis preventing NPC from distant metastasis. A group of 52 patients presenting with metastatic NPC were selected and strictly paired one-to-one, in sex, age, T stage, and N stage, with another 52 patients with non-metastatic NPC, who had survived for a long time after therapy. The tumor tissues of all 104 patients were retrieved for computer-assisted, immunohistochemical analysis of tumor vasculature. Counts of the microvessels and the relative area of all microvessels per image were significantly higher in metastatic NPC than they were in curable, non-metastatic NPC, while the average area of the microvessels and their average perimeter of in metastatic NPC were smaller than in non-metastatic disease. No significant difference in any microvessel parameter was found among the various types of metastasis. The alterations of microvessel parameters were significantly linked to the metastasis of NPC. Evaluation of neovascularity by computer image analysis may be helpful in estimating the prognosis of NPC and in determining the indicators for aggressive multimodal treatments.
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PMID:Primary study of neovasculature correlating with metastatic nasopharyngeal carcinoma using computer image analysis. 962 Feb 24

Monoclonal antibodies (MAbs), produced for specific tumor antigens, can be linked with radioisotopes or metabolic toxins and administered intraperitoneally (i.p.) to treat metastatic cancer located on the peritoneum. Despite their specific binding properties, these proteins distribute to the serosal surface of all tissues surrounding the cavity in the same manner as other serum proteins. Recent data have raised a problem of access of the solution containing the MAb to significant portions of the peritoneal surface. If the MAb does arrive at the surface of the tumor, it penetrates via diffusion and convection. The rapidity and depth of penetration of the MAb are very dependent on the binding characteristics of the MAb to the tumor cells. Current data indicate that tumors often have a large interstitial space relative to normal muscle, and this can accelerate both diffusion and convection. However, a highly permeable tumor vasculature in the absence of lymphatic drainage has also been shown to produce interstitial pressure gradients from the center toward the periphery of the tumor, setting up a potential outward flow which may be a significant barrier to the movement of MAbs into the nodule. While theoretical mechanisms of diffusion, convection, and binding are well established, there is still a great need for in vivo data.
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PMID:Tissue-level transport mechanisms of intraperitoneally-administered monoclonal antibodies. 974 14

Flavone acetic acid, an agent which has been implicated in both tumor vasculature collapse and NK cell activations, has been tested recently as a potential anti-cancer chemotherapeutic agent. We have tested this agent in combination with adoptive immunotherapy using IL-2 activated natural killer (A-NK) cells in a metastatic B16 melanoma model in C57BL/6 mice. By using rhodamine-labeled A-NK cells we have been able to quantitate both the number of A-NK cells that localize within each tumor section and the percentage of the tumor area occupied by A-NK cells. This has been accomplished using an image analysis system. Flavone acetic acid (200 mg/kg, i.p.) given one day prior to the injection of A-NK cells increased the area of the tumor occupied by A-NK cells and the area of individual A-NK cells approximately 2-fold; however, it did not appear to increase the number of A-NK cells per tumor cross-section. Nevertheless, this increase did not lead to any significant change in the therapeutic efficacy of A-NK cell adoptive immunotherapy. Our studies therefore suggest that mere enhancement of A-NK cell recruitment into tumor metastases does not necessarily translate into enhanced metastatic therapeutic efficacy. Moreover, this method may be a useful tool for pre-screening of compounds which enhance the accumulation of adoptively transferred cells into tumor metastases prior to in vivo screening for therapeutic efficacy.
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PMID:Flavone acetic acid enhances accumulation of IL-2 activated NK cells within established metastases. 989 Dec 22


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