Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1658953 (tumor vasculature)
 2,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PDT is a technique in which visible light is used in combination with photosensitizing agents to achieve a tumoricidal effect. Hematoporphyrins are the most commonly used photosensitizers in clinical practice. DHE is the active fraction of hematoporphyrin. Intravenously injected DHE is found in highest concentration in the liver followed by the spleen, kidney, tumor, skin, muscle, brain, and lungs. The strongest absorption bands for DHE are in the blue region of the spectrum, and this helps to account for the skin toxicity associated with PDT. Red light, at the wavelength of 630 nm, is usually used clinically because of its greater tissue penetration. Techniques such as photobleaching and use of photosensitizers that have weak absorption bands at the lower wavelengths may reduce cutaneous toxicity in the future. Other approaches, such as the use of monoclonal antibody-linked photosensitizers or cationic photosensitizers that are specifically localized in tumor cells, may also increase the effectiveness of PDT while decreasing toxicity. Light for PDT is usually provided by argon-pumped dye lasers or metal vapor lasers. Diode lasers will be used in the future. The use of fiber-optics and diffusing lenses allows the endoscopic and interstitial use of PDT. The mechanism of action of PDT involves the formation of singlet oxygen, which oxidizes biologic molecules and causes irreversible subcellular damage. The major in vivo effect of PDT is caused by its destruction of tumor vasculature, causing anoxia and necrosis. The use of PDT in gynecology has been limited. Several investigators have reported mixed results in treating lower genital tract intraepithelial and recurrent malignant tumors using a variety of approaches involving PDT. The use of PDT in other similar, though nongynecologic, tumors offers a direction for future research.
Obstet Gynecol Clin North Am 1991 Sep
PMID:Photodynamic therapy in gynecology. 195 68

Immunoconjugates of monoclonal antibodies with drugs, isotopes, or toxins are currently being investigated for their therapeutic effect on tumors. However, all have problems of access of the immunoconjugate to the tumor, particularly with solid tumors. To address this problem, we have used aminopterin-monoclonal antibody (AMN-mAb) conjugates combines with murine tumor necrosis factor (mTNF-alpha), which is known to have specific effects on tumor vasculature. In a murine model, well-established tumors (measuring 1.0-1.4 cm in diameter) were either totally eradicated or considerably reduced in size with combined therapy--a greater effect than with either mTNF-alpha or AMN-mAb used alone. The mechanisms involved in the improved antitumor effect were investigated using in vitro assays, autoradiography, and biodistribution experiments. mTNF-alpha was found both to increase the cytotoxic activity of the conjugate in vitro and to increase in vivo tumor localization of mAb up to 5-fold. The timing of mTNF-alpha administration was crucial to effects on tumor localization; mTNF-alpha given with mAb caused the greatest increase in localization and mTNF-alpha given well before mAb decreased localization. mTNF-alpha also reduced the toxicity to mice of AMN-mAb depending on the timing of injection. These results indicate that mTNF-alpha has a useful role in potentiation of immunoconjugate therapy but shows the need for careful planning of the dose regimen.
Cancer Res 1990 Sep 15
PMID:Effect of tumor necrosis factor on the antitumor efficacy and toxicity of aminopterin-monoclonal antibody conjugates: parameters for optimization of therapy. 239 67

Twelve patients with malignant brain tumors who had failed to respond to conventional therapies were treated with thermotherapy. Hyperthermic temperatures (approximately 43 degrees C) were induced in the tumors using microwaves at a frequency of 2450 MHz that were guided into the tumors by one or more semirigid coaxial applicators. These applicators fit into 16 gauge tubes or needles and can be inserted into the brain with minimal damage to healthy tissues. During each treatment, the tumors were maintained at hyperthermic temperatures for 1 hour. Several treatments spaced a few days apart were usually administered. The procedure used for producing hyperthermia in brain tumors with microwaves proved to be safe and could be repeated several times without producing toxic effects. Objective tumor responses were obtained in 75% of the patients (decrease in tumor size, 3 patients; slowing of tumor growth, 2 patients; necrosis of tumor tissues verified by pathological examination, 4 patients). Favorable clinical responses were observed in 75% of the patients (rapid decrease in intractable headaches, 5 patients; improvements in clinical deficits, 4 patients). Also, in all patients, the microwave power required to heat for a given time or a given volume decreased during most of the thermotherapy sessions, possibly because of heat damage to the tumor vasculature. Our results, taken together with the results of other investigators, indicate that thermotherapy is a promising modality for treating malignant brain tumors, either as the sole therapy or in combination with radiotherapy and chemotherapy. The next logical steps would be Phase I/II type trials of subjects whose disease is less advanced than the disease of patients treated in the current series of investigations.
Neurosurgery 1985 Sep
PMID:Microwave hyperthermia for brain tumors. 299 66

Angiogenesis is required for the progression of chronic inflammation, and agents that alter it can affect the development of inflammation and the consequent tissue destruction. However, in vivo quantification of neovascularization and its modulation by angiostatic and angiogenic agents is difficult. Studies have relied on reported effects of drugs on embryonic and tumor vasculature to infer angiomodulatory actions. We have characterized a vascular casting method that incorporates carmine in gelatin. Vascularity expressed as micrograms dye/mg dry tissue (vascularity index, V.I.) was studied in the murine chronic granulomatous air pouch. Carmine was retained within the vasculature by gelatin, and its content increased before the granulomatous tissue, resulting in a V.I. peak at 5 days, regression and a second peak over 14 to 28 days. The modulation of prostaglandin synthesis, plasma exudation and vasomotor tone showed that the carmine V.I. remained unaffected, unlike Evans blue, illustrating independence from acute inflammatory processes such as vasomotor tone and plasma exudation. The angiogenic stimulus p.o. heparin increased the V.I., whereas a sub-anti-inflammatory dose of cortisone with 1000 U heparin reduced it. Higher doses of heparin overcame this. The potent angiostatic steroid tetrahydrocortisol significantly reduced the V.I. in the absence of heparin. Cortisone exhibited independence from heparin on topical administration in hyaluronan. Dexamethasone inhibited granulomatous tissue development with a resulting increase in V.I. These observations indicated the differential effects of angiostatic and anti-inflammatory steroid activity. The pharmacological modulation of angiogenesis in inflammation can therefore be quantified.
J Pharmacol Exp Ther 1995 Sep
PMID:The pharmacological modulation of angiogenesis in chronic granulomatous inflammation. 756 23

Successful delivery of effector cells to tumor vasculature and the expression of cellular activities, such as extravasation and tumor infiltration are important aspects of the immune intervention of neoplastic disease. The structural rigidity of the effector cell, an indication of its cytoskeletal characteristics, plays an important role in influencing cellular functions and hemodynamic behavior as well as systemic distribution. The present study was designed to identify an agent which can modify the viscoelastic properties of human natural killer cells. A reducing compound, thioglycollate (TGA), was found to be an effective agent. Changes in cellular rigidity with respect to dose and duration of treatment with TGA were quantified. Micropipet aspiration was used to measure the resistance of NK cells to an imposed external deformation. Cultures of adherent human NK cells were expanded in interleukin 2 (IL-2) for 14 days, removed from culture and resuspended in medium with IL-2 and selected concentrations of TGA ranging from 0.032 mg/ml to 0.250 mg/ml. At 24 h intervals, the cell samples were removed and tested for their viscoelastic properties. Following 24 h of incubation, only TGA at 0.032 mg/ml produced a significant increase in cellular deformability. At 48 h of incubation, NK cell deformability was twice that obtained at 24 h. Higher concentrations of TGA also produced increased deformability after 48 h of incubation. Following 72 h of incubation, all concentrations of TGA tested produced increased deformability; however, the 0.032 mg/ml concentration produced the highest level of deformability combined with high viability (> 95%) as well as activated cell morphology. This treatment did not significantly alter the cytotoxic activity of these cells against a sensitive tumor target cell. These findings indicate that short term culture with TGA may be used to significantly reduce NK cell rigidity without decreasing cell viability or function. Thus, TGA may be a useful compound for altering the rheological properties of activated lymphocytes prior to adoptive transfer.
J Immunol Methods 1994 Sep 30
PMID:Reduction of rigidity in human activated natural killer cells by thioglycollate treatment. 793 Jun 40

The level of expression of the alpha 5/beta 1 integrin fibronectin receptor (FnR) strongly affects the growth rate of CHO cell tumors in nude mice. Here we report that alpha 5/beta 1 expression also influences the organization of the tumor vasculature. Tumors formed from CHO clones defective in FnR expression have a leaky vasculature that gives them a hemorrhagic appearance. Tumors from wild-type CHO cells, or from FnR-deficient CHO clones transfected with constructs coding for the alpha 5 integrin subunit, have an intact, non-leaky vasculature. In tumors from FnR-deficient cells, the endothelial lining of blood vessels is sparse, and red cells and plasma proteins can be detected in the tumor parenchyma. In tumors from cells expressing the alpha 5/beta 1 FnR, tumor vessels are circumscribed by a lining of von-Willebrand-factor-positive endothelial cells, and blood cells and proteins are confined to the vessel lumina. Thus, the level of expression of the alpha 5/beta 1 FnR in the tumor parenchymal cells can influence the development of tumor vasculature. Since alpha 5/beta 1 is vital to the organization of the extracellular matrix, one possibility is that altered matrix assembly contributes to the defective vascularization seen in alpha 5/beta 1-deficient tumors.
Int J Cancer 1993 Sep 30
PMID:Defective vasculature in fibronectin-receptor-deficient CHO cell tumors in nude mice. 837 28

Localization of activated natural killer (A-NK) cells in the microvasculature of growing tumors is the result of recognition of the intracellular and vascular cell-adhesion molecules ICAM-1 and VCAM-1 on the tumor endothelium, mediated by lymphocyte function-associated protein LFA-1 and vascular lymphocyte function-associated protein VLA-4. In vitro and in vivo studies of A-NK cell adhesion to endothelial cells showed that vascular endothelial growth factor (VEGF) promotes adhesion, whereas basic fibroblast growth factor (bFGF) inhibits adhesion through the regulation of these molecules on tumor vasculature. Thus, some angiogenic factors may facilitate lymphocyte recognition of angiogenic vessels, whereas others may provide such vessels with a mechanism that protects them from cytotoxic lymphocytes.
Nat Med 1996 Sep
PMID:During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium. 878 49

Due to the high permeability of tumor vessels to fluids and plasma proteins, the microvascular pressure (MVP) is the principal driving force for interstitial hypertension in solid tumors; as a result, hydrostatic pressures between the microvascular and interstitial space are close to equilibrium. Based on these observations, we hypothesized that the tumor interstitial fluid pressure (IFP) should increase following the onset of angiogenesis. To this end, the relationship between IFP and tumor neovascularization was determined in the human colon adenocarcinoma (LS174T) and the murine carcinoma (MCaIV) implanted in a transparent dorsal skin fold chamber in severe combined immunodeficient mice. Three stages in the development of the tumor neovasculature were characterized by intravital microscopy. Stage I tumors were avascular, stage II was characterized by vascular sprouts and loops, and in stage III, the tumor vasculature was completely developed and blood flow was obvious. The IFP was measured with micropipettes and a servo-null system. For both tumor types, the IFP in stage I tumors was close to 0 mm Hg, and IFP increased significantly from one stage to the next. To further confirm that interstitial hypertension was associated with the development of the tumor vasculature, IFP was measured in LS174T spheroids. The mean pressure in spheroids was 0.2 +/- 0.3 mm Hg. In stage III tumors, the IFP was compared to the MVP. In MCaIV, the MVP was comparable to the IFP; however, in LS174T the MVP was significantly higher than the IFP. In conclusion, the results demonstrate that avascular tumors have atmospheric pressures and that tumor interstitial hypertension is associated with the development of the neovasculature.
Cancer Res 1996 Sep 15
PMID:Tumor angiogenesis and interstitial hypertension. 879 2

The effects of intralesional injection of newly synthesized natural-type human tumor necrosis factor (nh-TNF) on experimental brain tumors in rats were investigated. The repeated injection of 5,000 U of nh-TNF into the tumor resulted in the prolongation of the survival time of the rats. More than half of the nh-TNF treated tumors were red, and were characterized by histopathological features of marked congestion of tumor vessels. Fibrin formations were also found in the tumor vessels. These histological findings were not observed in the control tumors. Furthermore, coagulative necrosis was observed in the center of some reddish tumors. Leukocytes adhering to vascular endothelium and infiltration of the leukocytes were also observed in the tumors of nh-TNF treated rats. In the immunohistochemical examination, these infiltrated cells were primarily polymorphonuclear leukocytes and macrophages. Expression of intercellular adhesion molecule-1 (ICAM-1) increased on the tumor endothelial cells after the administration of nh-TNF. These results suggest that repeated injection of nh-TNF has a therapeutic effect on brain tumors through its extensive influences on tumor vasculature.
J Vet Med Sci 1996 Sep
PMID:Antitumor activity of natural-type human tumor necrosis factor on experimental brain tumors in rats. 889 88

The mechanisms by which interleukin-12 (IL-12) exerts antitumor effects have been difficult to dissect. In this study, we examined the potential contribution of the chemokines interferon-gamma-inducible protein-10 (IP-10) and Mig to the antitumor effects of IL-12. Using an athymic mouse model, local inoculations with IL-12 consistently produced tumor size reductions associated with characteristic tumor necrosis and vascular damage. These effects were indistinguishable from those produced by IP-10 or Mig injected locally in the same tumor model. Local and systemic treatment with IL-12 was associated with expression of the interferon-gamma (IFN-gamma), IP-10, and Mig genes and proteins in the tumor. Levels of IP-10 and Mig expression in the tumor, the liver, and the kidney were inversely correlated with tumor size. Administration in vivo of neutralizing antibodies to IP-10 and Mig reduced substantially the antitumor effects of IL-12 inoculated locally into the tumors. These results support the notion that IP-10 and Mig contribute to the antitumor effects of IL-12 through their inhibitory effects on tumor vasculature.
J Leukoc Biol 1998 Sep
PMID:Contribution of the CXC chemokines IP-10 and Mig to the antitumor effects of IL-12. 973 66


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