Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesive interactions between lymphocyte cell-surface receptors and components of the vascular endothelium and the extracellular matrix play an important role in the control of lymphocyte migration and homing. To investigate whether lymphocyte adhesion molecules involved in the migration of normal lymphocytes, i.e., CD44 homing receptor, LFA-1 (CD11a/18), and ICAM-1 (CD54), also play a role in the spread and hence in the disease course of non-Hodgkin's lymphomas (NHL), expression of these molecules was examined in 78 cases of diffuse large-cell lymphoma. Other potential risk factors considered in this study were sex, age, primary tumor localization, lineage (T cell vs. B cell), and histopathological subtype. 27 of 53 (51%) patients with a lymphoma having a high CD44 antigen expression showed tumor spread beyond stage II at diagnosis while this was the case in only three of 25 (12%) patients with lymphomas that were CD44 low/negative (chi-square 25.4, p less than 0.001). Similarly, poor response to treatment, i.e., absence of remission or relapse, and or death from lymphoma, was more common among patients with lymphomas expressing high levels of CD44; actuarial survival among patients with CD44 high and low lymphomas was 47% and 91%, respectively (Mantel-Cox 6.1, p = 0.02). Neither LFA-1 nor ICAM-1 expression showed a significant correlation to lymphoma dissemination or disease course. Of the other factors considered, T cell phenotype was associated with an unfavorable prognosis while nodal localization was a risk factor for dissemination. Taken together, our findings suggest that CD44 antigen expression plays an important role in the dissemination of NHL and via this mechanism exerts an unfavorable prognostic influence.
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PMID:Adhesion molecules in the prognosis of diffuse large-cell lymphoma: expression of a lymphocyte homing receptor (CD44), LFA-1 (CD11a/18), and ICAM-1 (CD54). 197 38

Cancer cell detachment in three distinct and critical parts of the metastatic cascade is discussed. The detachment of cancer cells from their parent tumors is an initial early event in metastasis. The site of detachment with respect to proximity to blood vessels may determine the initial dissemination route. Many factors affect cell detachment; we specifically consider the effects of growth-rate, necrosis, enzyme activity, and stress on cell release in terms of metastasis-promoting mechanisms. Detachment is also discussed in relation to active cancer cell locomotion, where localized detachment from the substratum is a prerequisite for translatory movement. The importance of active cell movement in tissue invasion has only recently been assessed, and, in the case of at least some human malignant melanomas, a zone of actively moving cancer cells is believed to precede the growing body of the tumor. The secondary release of cancer cells from temporary arrest sites at the vascular endothelium consequent upon intravascular dissemination is also a major area of investigation. Circulating cancer cells arrest at vascular endothelium or are impacted in small vessels, however, most are released into the circulation and subsequently perish. The blood stream is a hostile environment, and it is probable that cancer cells are sufficiently damaged in translocation by hemodynamic trauma and humoral factors such that they easily detach or are 'sheared-off' the vascular endothelium by blood flow. Another possibility is that in some cases they are processed by 'first organ encounters' and perish before or shortly after arriving in a second organ. Animal studies have shown that, following intravenous injection, 60-100% of the injected dose of viable cancer cells are initially arrested in the lungs, but very few remain after 24 hr. As it is only those retained cells which produce tumors, the mechanisms involved in this secondary release, which occurs in all organs so far examined, are critical to any understanding of the metastatic cascade and metastatic inefficiency. The arrest of cancer cells at the vascular endothelium and their subsequent release have been associated with the presence of platelets, and the deposition of fibrin and manipulation of platelet-aggregating mechanisms and fibrinolysis are discussed in terms of their antimetastatic effects. The role of the reticuloendothelial system, natural killer cells, and polymorphs is discussed in relation to cancer cell clearance from blood vessels and also to inherent cancer cell properties which may act to inhibit their metastasis. Although detachment of cancer cells from a primary tumor may be regarded as metastasis promoting, secondary release of cancer cells may be associated with inhibition of metastasis.
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PMID:Cell detachment and metastasis. 635 10

Angiogenesis quantitation of 106 patients with primary breast cancer and 35 patients with adenofibroma of the breast was compared and examined to its prognostic relevance for five-years disease-free survival in breast cancer patients. Immunocytochemical staining for Factor VIII-related antigen was performed to outline vascular endothelium. We found a significant higher vessel density in breast cancer patients who experienced recurrence (17.4) than in those with no recurrence (9.4) or with adenofibroma (8.7) [p < 0.0001]. The probability of five-years recurrence-free survival for patients with a primary tumor of high vessel density was at 52.3% and 86.4% for tumors of low microvessel density (p < 0.0011). Microvessel density proved to be an independent prognostic factor for breast cancer recurrence in the Cox-Model (relative risk 2.047, p = 0.0002).
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PMID:[Tumoral vascular density in breast tumors and their effect on recurrence-free survival]. 753 24

At present the most used method to quantify tumor angiogenesis in human solid tumors is the count of intratumoral microvessels in the primary lesion. This method requires the use of specific markers to vascular endothelium and of immunohistochemical procedures to visualize microvessels. Several studies have found that intratumoral microvessel density (IMD) determined in the primary tumor is significantly associated with metastasis and prognosis in some solid neoplasia, particularly in operable breast carcinoma. The subjective evaluation of IMD made by two observers at the microscope is rapid and of low cost, but presents some difficulties, mainly the identification of the most vascularized area ("hot-spot") within each tumor. This method can be improved upon to attain a better reproducibility among different pathologists. For example, the use of a multiparametric computerized image analysis system (CIAS) seems to be a promising tool to improve accuracy, feasibility and reproducibility of microvessel counts, although there are still some open technical problems to completely automate its use. Angiogenic activity is the result of a balance between angiogenic stimuli and angio-inhibition. Therefore the determination of angiogenic peptides and/or natural angiogenesis inhibitors in the tumor tissue, serum, or urine of cancer patients seems to be a promising alternative to microvessel counting. At present it is possible to determine the expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and transforming growth factor beta using immunohistochemical methods. Serum and urine levels of bFGF can be assessed using an immunoenzymatic assay. Methods used to assess the expression and levels of urokinase-type plasminogen activator (uPA) or plasminogen activator inhibitor-1 (PAI-1) have also been developed, and correlate with angiogenic activity and prognosis of patients with breast cancer. Finally, some investigational methods to assess angiogenesis in vivo are presented and discussed. Angiogenesis is a very complex phenomenon. Thus it seems reasonable to hypothesize that its assessment by using concurrently several of the available methods may provide more valid, accurate, and comprehensive information on the angiogenic activity of each single tumor. For a reliable and reproducible assessment of angiogenesis for all of the assays, validation procedures and quality control protocols are mandatory.
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PMID:Novel methods for the determination of the angiogenic activity of human tumors. 853 66

The ability of a tumor cell to survive is critical for successful dissemination to sites distant from the primary tumor. Tumor cells must enter blood circulation, resist hemodynamic shear stress of the blood circulation, successfully extravasate, and then migrate through dense tissue stroma to a site favorable for tumor growth. Some tumor cells must therefore be endowed with peculiar abilities to successfully metastasize, whereas others, although capable of forming tumor in specific organs, cannot metastasize. This property has often been associated with the homing ability of a given tumor cell, likely through the expression of organ-specific homing receptors that are critical for the extravasation process. The present work was aimed at establishing the point at which metastatic and nonmetastatic lymphoma cells diverge. Although 164T2 and 267T2 lymphoma cell lines can successfully form thymic lymphoma when injected intrathymically, only the 164T2 clone can efficiently form tumor in kidneys, spleen, and liver after intravenous inoculation. Using the indium-labeling technique to monitor the homing kinetic of both cell lines, we showed that the critical step for the successful metastasis of the lymphoma cell was determined in the final steps of the disseminating process, namely after homing. These results indicate that, whereas binding of tumor cells to vascular endothelium through specific adhesion mechanisms is a prerequisite for dissemination of tumor cells, the resistance of a tumor cell to the antagonist action of the host and/or its ability to grow tumor occurs only after homing to the target organ.
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PMID:The metastatic characteristics of murine lymphoma cell lines in vivo are manifested after target organ invasion. 942 18

Canine osteosarcoma is a prevalent bone neoplasm which has similarities to the human disease. We used a retrospective study to investigate the possibility that tumor vascularity may provide useful prognostic information, indicative of the role of this parameter in progression of this cancer. We quantified microvessel density in 52 histological specimens of primary tumor, immunostained for von Willebrand's Factor to identify vascular endothelium. For the 20 cases not euthanized at presentation or lost to follow-up, we found significantly higher tumor microvascular densities in animals presenting with detectable pulmonary metastases (5 of 20), and significantly lower densities in animals without metastatic disease at presentation, but later surviving to develop pulmonary metastases (7 of 20; P < 0.05). Animals with no evidence of pulmonary metastases at time of death (8 of 20) had intermediate vascular densities in their tumors. The results of this preliminary study suggest that vascularity of the primary tumor may be an indication of tumor progression. Future studies with a larger number of cases should establish whether vascular density can be a useful prognostic parameter for canine osteosarcoma.
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PMID:Blood vessel density in canine osteosarcoma. 968 49

Integrins are receptors that mediate cell adhesion and the formation of signaling complex. Changes in the expression of integrins are required during the following steps in the generation of metastases: a) angiogenesis; b) detachment from the primary tumor; c) tumor cell-platelet interaction; d) adhesion to vascular endothelium and e) proliferation. There is a correlation between invasive capability and changes in the expression of some proteins that are clustered in focal adhesion sites, as FAK, CD82, CD9 or CD63. Both, integrin blocking (using antibodies or RGD containing peptides), as well as induced changes in the expression of integrin-associated molecules, are able to inhibit formation of metastases. Discovery and characterization of molecules that regulate the adhesive capability of tumor cells, will lead to development of antimetastasic therapies. In the search of tumor dissemination inhibitors, integrins and some integrin-associated molecules are important pharmacological targets.
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PMID:[Integrins and integrin-associated molecules: targets for the development of antimetastatic therapies]. 1046 9

An eight-year-old, male castrated bullmastiff presented to the Kansas State University Veterinary Medical Teaching Hospital with left hind-limb paralysis. A mass was identified in the left paralumbar soft tissue adjacent to the fourth (L4) to sixth (L6) lumbar vertebrae by magnetic resonance imaging. The iliopsoas muscle contained the mass which was identified as a hemangiosarcoma on histopathological examination. Hemangiosarcoma is rarely reported as a primary tumor arising from muscle vascular endothelium.
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PMID:Primary hemangiosarcoma of the iliopsoas muscle eliciting a peripheral neuropathy. 1073 Jun 28

Anti-vascular treatment by targeting proliferating endothelial cells has become a promising option in anti-neoplastic therapy. Combretastatin A-4 prodrug (CA-4PD) has been identified as a selective inhibitor of endothelial cell proliferation, acting by the interruption of microtubule assembly. In this study, the effect of CA-4PD on proliferating endothelial cells derived from a primary tumor of the vascular endothelium was investigated in vitro and in vivo. In vitro, CA-4PD was an effective inhibitor of endothelial cell proliferation in a time- and dose-dependent manner, displaying a certain selectivity toward endothelial cells in comparison to proliferating fibroblasts. Analysis of DNA profiles by FACS revealed an increasing proportion of cells arrested in the G(2) cell-cycle phase with correlation to the duration of drug exposure. A decrease in cell viability correlated with duration of drug exposure, whereas FACS analysis, DNA fragmentation assay, and DNA gel electrophoresis failed to demonstrate that DNA fragmentation was indicative of apoptosis up to 48 hr of continued drug exposure. In vivo, CA-4PD induced excessive regressive alterations in experimentally allotransplanted hemangioendotheliomas within 24 hr after singular i. p. injection of 100 mg CA-4PD/kg body weight. This represented less than one-tenth of the maximum tolerated dose. In conclusion, our findings characterize CA-4PD as a potent inhibitor of malignant endothelial cell proliferation in vitro, effecting arrest of proliferating cells in the G(2) cell-cycle phase with subsequent cell death on a pathway different from apoptosis. in vivo, CA-4PD induces extensive intratumoral cell loss within 24 hr following systemic administration, suggesting a synergistic effect of direct cell killing and the induction of vascular shutdown.
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PMID:Combretastatin A-4 prodrug: a potent inhibitor of malignant hemangioendothelioma cell proliferation. 1095 95

The glutathione (GSH) content of cancer cells is particularly relevant in regulating mutagenic mechanisms, DNA synthesis, growth, and multidrug and radiation resistance. In malignant tumors, as compared with normal tissues, that resistance associates in most cases with higher GSH levels within these cancer cells. Thus, approaches to cancer treatment based on modulation of GSH should control possible growth-associated changes in GSH content and synthesis in these cells. Despite the potential benefits for cancer therapy of a selective GSH-depleting strategy, such a methodology has remained elusive up to now. Metastatic spread, not primary tumor burden, is the leading cause of cancer death. For patient prognosis to improve, new systemic therapies capable of effectively inhibiting the outgrowth of seeded tumor cells are needed. Interaction of metastatic cells with the vascular endothelium activates local release of proinflammatory cytokines, which act as signals promoting cancer cell adhesion, extravasation, and proliferation. Recent work shows that a high percentage of metastatic cells with high GSH levels survive the combined nitrosative and oxidative stresses elicited by the vascular endothelium and possibly by macrophages and granulocytes. ?-Glutamyl transpeptidase overexpression and an inter-organ flow of GSH (where the liver plays a central role), by increasing cysteine availability for tumor GSH synthesis, function in combination as a metastatic-growth promoting mechanism. The present review focuses on an analysis of links among GSH, adaptive responses to stress, molecular mechanisms of invasive cancer cell survival and death, and sensitization of metastatic cells to therapy. Experimental evidence shows that acceleration of GSH efflux facilitates selective GSH depletion in metastatic cells.
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PMID:Glutathione in cancer biology and therapy. 1651 21


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