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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of photodynamic therapy tumor destruction is dependent upon both the interruption of the tumor vasculature and the resultant production of unstable oxygen species causing cellular oxidation and death. Chloroaluminum sulfonated phthalocyanine (CASP) is a recently developed photosensitizer. In order to study the direct vascular effects of CASP on a non-tumor system, a rat window chamber was utilized. Twelve rats were implanted with the window chamber, and were divided into two groups of six. Three rats served as controls for each group (receiving light alone, CASP alone, or no treatment). The remaining 6 rats received 10 mg/kg CASP intravenously 4 days after chamber placement. Photoactivation with light was performed 24 hours after injection (power density 200 mW/cm2, irradiance 100 J/cm2, lambda = 675 nm). Utilizing integrating sphere measurements and image analysis, marked vascular changes in the form of initial vasospasm followed by vaso-constriction and loss of chamber neovascularization were noted in the CASP-PDT group. The control groups exhibited no significant changes. Manipulation of the chamber vasculature at strategic time-points may translate into improved response rates for photodynamic therapy in a tumor model.
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PMID:Photodynamic therapy with chloroaluminum sulfonated phthalocyanine in the rat window chamber. 169 40

Anti-tumor antibody (317G5) covalently coupled to an anti-CD3 antibody (OKT3) produces a heteroaggregate (HA) antibody that can target PBL to lyse tumor cells expressing the appropriate tumor Ag. The i.v. and i.p. distribution of radiolabeled HA antibody 317G5 x OKT3 and of radiolabeled cultured human PBL were studied in athymic nude mice bearing solid intraperitoneal tumor established from the human colon tumor line, LS174T. Mice were injected with 125I-labeled HA antibody, 125I-labeled anti-tumor mAb, or 111In-labeled PBL, and at designated timepoints tissues were harvested and measured for radioactivity. 125I-317G5 x OKT3 localized specifically to tumor sites. Tumor radioactivity levels (percent injected dose/gram) were lower with 125I-317G5 x OKT3 HA antibody than with 125I-317G5 anti-tumor mAb, but were similar to levels reported for other anti-tumor mAb. The major difference in radioactivity levels observed between i.v. and i.p. administration of 125I-317G5 x OKT3 was an increase in hepatic radioactivity after i.v. HA antibody administration. HA antibodies produced from F(ab')2 fragments, which exhibit decreased m. w. and decreased Fc receptor-mediated binding, demonstrated improved tumor:tissue ratios as compared to intact antibody HA. 125I-317G5 F(ab')2 x OKT3 F(ab')2 antibody levels were equivalent to intact HA antibody levels in tumor, but were lower than intact HA antibody levels in the blood, bowel, and liver. Tumor:bowel ratios (20:1 at 48 h) were highest when 317G5 F(ab')2 x OKT3 F(ab')2 was injected i.p. Autoradiography confirmed that anti-tumor x anti-CD3 HA antibodies localized specifically to intraperitoneal tumor; that i.p. administered HA antibodies penetrated tumor directly; and that i.v. administered HA antibodies distributed along tumor vasculature. Cultured human PBL distributed in moderate concentrations to intraperitoneal tumor when administered i.p., but not when administered i.v. The poor localization of i.v. injected PBL to tumor may reflect species disparity in homing receptors and/or endothelial ligands, a problem which may be overcome with a syngeneic model. These results suggest that regional therapy with HA antibodies and PBL may offer advantages over systemic therapy for initial clinical trials.
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PMID:Regional and systemic distribution of anti-tumor x anti-CD3 heteroaggregate antibodies and cultured human peripheral blood lymphocytes in a human colon cancer xenograft. 170 13

The structure and function of the tumor microvasculature is of great interest for cancer biology, diagnosis, and therapy. The distribution of endothelial cells, pericytes, and basal lamina in tumors is not well documented. In this study, the authors investigated the distribution of markers for these different components in a series of malignant human tumors and in human granulation tissue, both situations with extensive angiogenesis. Their results show a striking heterogeneity in the expression of markers for pericytes and endothelial cells between different tumors, but also within a single tumor lesion. To be able to distinguish between these two adjacent cell types decisively, all marker studies were carried out both on the light and the electron microscopical level and compared with staining results in granulation tissue of cutaneous wounds in healthy volunteers and of decubitus lesions. In granulation tissue of decubitus lesions, well-defined zones with increasing levels of maturation can be delineated. It was found that antibodies recognizing von Willebrand factor often failed to stain the tumor capillaries. Of the pericyte markers, alpha-smooth muscle actin was only locally expressed by pericytes in the tumor vasculature, whereas the high-molecular-weight melanoma-associated antigen, a chondroitin sulfate proteoglycan, stained the microvasculature broadly. Staining of the basal lamina components collagen type IV and laminin was, within the tumor, not restricted to the microvasculature. From their findings the authors conclude that 1) for the visualization of the tumor vasculature, antibodies recognizing endothelial markers, especially monoclonal antibodies PAL-E and BMA 120, are preferable to those recognizing pericytes or basal lamina; 2) within the microvasculature of tumors and granulation tissue, a heterogeneity of expression of endothelial and pericyte markers is observed; 3) during the formation of granulation tissue, all three microvascular components can be demonstrated already in the histologically earliest stage, suggesting not only an involvement of endothelial cells but also of pericytes and basal lamina in the initial steps of angiogenesis in wound healing.
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PMID:Differential expression of markers for endothelial cells, pericytes, and basal lamina in the microvasculature of tumors and granulation tissue. 171 Dec 88

Delivery of monoclonal antibodies to solid tumors is a vexing problem that must be solved if these antibodies are to realize their promise in therapy. Such success as has been achieved with monoclonal antibodies is attributable to the local hyperpermeability of the tumor vasculature, a property that favors antibody extravasation at tumor sites and that is mediated by a tumor-secreted vascular permeability factor. However, leaky tumor blood vessels are generally some distance removed from target tumor cells, separated by stroma and by other tumor cells that together represent significant barriers to penetration by extravasated monoclonal antibodies. For this reason, alternative approaches may be attractive. These include the use of antibody-linked cytotoxins, which are able to kill tumor cells without immediate contact, and direction of antibodies against nontumor cell targets, for example, antigens unique to the tumor vascular endothelium or to tumor stroma.
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PMID:Structure of solid tumors and their vasculature: implications for therapy with monoclonal antibodies. 171 64

The effects of intravenous (IV) infusion of human recombinant tumor necrosis factor-alpha (rTNF-alpha, Cetus) on normal brain and malignant glioma in rats were examined. Twelve Fischer 344 rats were given either a single injection of 10(6) U rTNF-alpha or injections of 5 x 10(5) U rTNF-alpha for three days. One day post-rTNF-alpha injection(s), rats were injected IV with horseradish peroxidase (HRP) to determine blood-brain barrier (BBB) breakdown and, one hour later, were perfused with an aldehyde fixative and processed for histologic examination. Treatment of normal rats with rTNF-alpha by either dosage or schedule caused no remarkable histopathologic changes in the brain and no alteration in BBB integrity. Human glioma models were produced by intracerebal inoculation of 10(4) syngeneic RT-2 glioma cells into the right parietal lobe of 30 rats. Animals received single IV injections of 10(6) U human rTNF-alpha or its excipient (TNF-E) as above on day 3, 7, or 10 post-tumor inoculation or multiple injections of 5 x 10(5) U rTNF-alpha beginning on day 7, 10, or 12 post-tumor inoculation. With a single IV injection of either rTNF-alpha or its excipient, 3-day models showed a similar pattern of HRP extravasation limited to the extracellular space of the tumor inoculation site. In 7-day models treated with a single IV injection of rTNF-alpha or TNF-E, HRP extravasated throughout the tumor, but did not exceed peritumoral margins. In 10-day models treated with a single injection of TNF-E, HRP was found only in the tumor and immediate peritumoral regions while rTNF-alpha-treated rats showed more extensive areas of BBB breakdown with HRP evident throughout the entire right hemisphere and extending via the corpus callosum into the contralateral hemisphere. Pericapillary halos were also evident around the small blood vessels within the edematous areas of the corpus callosum. Within tumors, hemorrhagic necrosis and adherence of neutrophils to vessels was observed only in animals treated with rTNF-alpha at 10 days post-tumor inoculation. Multiple IV injections of rTNF-alpha in 7 and 10-day models triggered widespread hemorrhagic necrosis, neutrophil adherence and infiltration in the tumor. There was also extravasation and diffusion of HRP from the site of glioma into the contralateral hemisphere. Twelve-day models treated with multiple rTNF-alpha injections, in addition, showed irregular luminal surfaces and gaps between adjacent endothelial cells of tumor vasculature.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute effects of human recombinant tumor necrosis factor-alpha on the cerebral vasculature of the rat in both normal brain and in an experimental glioma model. 171 71

Cancers have a formidable capacity to develop resistance to a large and diverse array of chemical, biologic, and physical anti-neoplastic agents. This can be largely traced to the instability of the tumor cell genome, and the resultant ability of tumor cell populations to generate phenotypic variants rapidly. It is therefore argued that anti-cancer strategies should be directed at eliminating those genetically stable normal diploid cells that are required for the progressive growth of tumors. Microvascular endothelial cells comprising the tumor vasculature represent such a normal cell target. Moreover, specificity for tumor associated vasculature by anti-cancer agents may be achieved by virtue of the fact that many of the endothelial cells that comprise these blood vessels are in an immature, cycling, and 'activated' state, in contrast to the endothelial cells associated with normal tissue and organ blood vessels.
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PMID:Inhibition of tumor angiogenesis as a strategy to circumvent acquired resistance to anti-cancer therapeutic agents. 172 75

Elevated interstitial fluid pressure (IFP) of tumors may be a physiological barrier to the delivery of certain therapeutic agents. The objective of this study was to find out if IFP could be lowered using localized hyperthermia and if the reduction in IFP could predict the tumor response to treatment. Amelanotic melanoma (A-Mel-3) implanted into the dorsal skin of Syrian golden hamsters was exposed to hyperthermic treatment after 7 days of tumor growth at tumor volumes of about 100-150 mm3. Hyperthermia was induced by immersing the tumor in a water bath at 43 degrees C for 30 or 60 min. Forty-eight h later the IFP of control and treated tumors was determined by using the wick-in-needle technique. The mean IFP in control tumors was 12.6 mmHg. Hyperthermic treatment for 30 min induced a significant decrease to 2.8 mmHg (P less than 0.001 versus controls), whereas a 60-min immersion of the tumors induced a further decrease to 0.8 mmHg (P less than 0.05 versus 43 degrees C for 30 min). Separate experiments on tumor growth in corresponding groups of animals revealed a significant growth delay of 2.7 days after hyperthermia for 30 min. Enhanced growth delay and partial tumor response in 66% of the tumors were found following 60 min of hyperthermia at 43 degrees C. The thermal dose-dependent decrease in IFP presumably results from the dose-dependent damage to the tumor vasculature. In addition, the association of an enhanced biological effect with a more pronounced reduction of interstitial fluid pressure suggests that the IFP might serve as a quantitative parameter to predict the response of tumors to hyperthermic therapy.
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PMID:Interstitial fluid pressure in solid tumors following hyperthermia: possible correlation with therapeutic response. 172 21

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

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.
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PMID:Photodynamic therapy in gynecology. 195 68

Oxygen pressure (pO2) in brain tumors, pO2 in brain cortex surrounding the tumors, and PaO2 were measured simultaneously during total resection in 16 patients with previously untreated brain tumors in order to detect hypoxic regions within the tumors. When the inhaled O2:N2O ratio was 1:3 under enflurane anesthesia, mean PaO2 was 109.2 +/- 5.8 mm Hg, a rather high value when compared with that obtained when air is inhaled under atmospheric pressure. The simultaneously measured intratumoral pO2 and pO2 in brain cortex surrounding the tumor were 15.3 +/- 2.3 and 59.8 +/- 6.5 mm Hg, respectively. Each intratumoral pO2 value was significantly lower than that of pO2 in brain cortex surrounding the tumor (mean less than 30 mm Hg, Wilcoxon signed rank test, p less than 0.005) and influenced the oxygen effects on radiation. These results appear to confirm that there are hypoxic regions within human brain tumors. A comparison between intratumoral pO2 and either the angiographic or contrast-enhanced computerized tomography scans of the tumor vasculature disclosed no correlation.
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PMID:Intratumoral oxygen pressure in malignant brain tumor. 198 7


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