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Sensitization of hypoxic tumor cells and control of growth thereof - Patent 4889525 Method of sensitizing hypoxic tumor cells to radiotherapy and chemotherapy by contacting the cells or the vasculature thereof with an aqueous dispersion of an oxygen carrying perfluoro compound and a dispersant for the compound, and sensitizing chemotherapeutic and protective compositions therefor. A method of controlling the growth of hypoxic tumor cells which comprises (a) sensitizing the cells to chemotherapy by contacting the cells with an aqueous dispersion of any oxygen carrying perfluoro compound and a dispersant for the perfluoro compound, and (b) contacting the cells with a chemotherapeutic agent whose efficacy is oxygen dependent. In accordance with the present invention effective sensitization of hypoxic tumor cells, as a prelude to highly beneficial radiotherapy and/or oxygen-dependent chemotherapy, is achieved by contacting the cells or vasculature thereof with an oxygen carrying perfluoro compound, wherein the perfluoro compound is uniformly dispersed in small particle size in an aqueous medium. www.freepatentsonline.com /4889525.html   (9951 words)

PRINCIPLES OF RADIATION ONCOLOGY(Jan.1997) Radiotherapeutic tumor control is achieved by the elimination of all viable cells within a tumor, and a given dose of radiation will result in the death of a certain proportion (not number) of viable cells with each administration. The sigmoidal shape of the curve is a result of the heterogeneity among the tumor cell population for a given neoplasm with regard to the number of viable tumor cells and the proportion of cells that are hypoxic. The concept is based on the notion that tumor cell killing by radiation is an exponential function of dose and that the dose required for a particular tumor control probability is proportional to the logarithm of the number of viable cells in the tumor. www.utmb.edu /otoref/Grnds/radther.htm   (4402 words)

Zhong Yun, PhD: Therapeutic Radiology Tumor hypoxia is strongly correlated with advanced disease stage and poor clinical outcome. This is, in part, due to increased genomic instability in hypoxic tumor cells and enhanced resistance of hypoxic tumors to radio- and chemo-therapy. Recently, increasing amounts of evidence suggest that hypoxic tumor cells tend to be poorly differentiated. info.med.yale.edu /therarad/faculty/yun.html   (1079 words)

Starve a tumor, or feed a tumor? Within a tumor, chaos reigns: Nutrients are scarce, and healthy tissue is muscled out by cancerous tissue so aggressive that the tumor even sacrifices parts of itself to continue its relentless expansion. Tumor cells that survive hypoxic conditions are often the cells that are most aggressive, most hardy, and most likely to go out and start new cancer colonies," he says. She has developed a fluorescent molecule that tags hypoxic regions within tumors, and she is working with doctors at the University of Pennsylvania to identify patients who have tumors that are hypoxic and may need different treatments than traditional radiation and chemotherapy. www.eurekalert.org /pub_releases/2003-09/uorm-sat091103.php   (1009 words)

NCI Drug Dictionary - National Cancer Institute In regional chemotherapy, absorbable gelatin sponge may be used to embolize arteries in the region of a tumor in order to block or retard blood flow; this blockage results in a locally increased concentration of chemotherapeutic agents delivered to the tumor when chemotherapeutic agents are infused into the embolized arterial circulation upstream of the blockage. Ad5CMV-p53 induces tumor cells that have been transfected with the vector to produce wild-type p53, a tumor suppressor gene that is deleted or mutated in a significant number of cancers. Tumor cells harvested from a patient are infected with ALVAC-hB7 1, thereby producing an autologous cell line that exhibits increased expression of HLA class I and class II, CD54 (ICAM), and CD80. www.cancer.gov /templates/drugdictionary.aspx?expand=All   (6891 words)

BioMed Central | Full text | Kinetic analysis of dynamic 18F-fluoromisonidazole PET correlates with radiation treatment ... Tumor control was defined on the basis of computed tomography (CT) scans as complete and persistent regression of the primary tumor and failure was defined as local recurrence of the tumor in the irradiated fields. All possible combinations of hypoxia and perfusion parameters were observed: well perfused tumors which were not at all hypoxic, tumors showing at the same time a quite high vascular density and hypoxic subareas, and finally also tumors that were badly perfused and severely hypoxic. The resistance of a hypoxic tumor to RT is governed, among others, by two factors: the initial magnitude of the hypoxic subpopulation of clonogenic cells, and the rate with which these cells are reoxygenated. www.biomedcentral.com /1471-2407/5/152   (4693 words)

ScienceDaily: Penn Researchers Create Drug To Help Target Attack On Cancerous Tumors Patients with early stage cervix tumors, located at the neck of the uterus, and soft tissue sarcomas, are given EF5 intravenously two days before their tumors are surgically removed or biopsied. A small portion of the tumor, removed at surgery, is then exposed to fluorescent monoclonal antibodies.* These antibodies fasten to the hypoxic regions in the tumor and highlight its oxygen content. Tumor suppressor gene -- A tumor suppressor gene is a gene that reduces the probability that a cell in a multicellular organism will turn into a tumor cell. www.sciencedaily.com /releases/1998/03/980302070943.htm   (1835 words)

Therapeutic Radiology and Oncology We are developing treatments that are minimally invasive and highly effective by utilizing physical energies (radiation, heat) or the technique of IVR for the eradication of malignant neoplasm, which is among the top causes of death of the Japanese. Tumor hypoxia has been considered to be a potential therapeutic problem because it renders solid tumors more resistant to sparsely ionizing radiation (IR) and chemotherapeutic drugs. The green indicates a blood vessel and the red indicates hypoxic tumor cells. www.med.kyoto-u.ac.jp /E/grad_school/introduction/1313   (1302 words)

The Revised Metabolic Oncolytic Regimen Hypoxic tumor cells will compensate for this compromised metabolic state of affairs by increasing the rate of intracellular glycolysis. When tumors are deprived of the ability to form new blood vessels, they fail to thrive and in at least some instances become encapsulated and experience partial or complete lysis (20). By day 12 of Phase II treatment the tumor was reduced 83.5% [The starting size of the tumor in Phase II was bigger than in Phase I. It is not known whether the tumor grew during the resting interval between treatment phases. www.all-natural.com /oncolytic.html   (6003 words)

PROJECT 1 Although one hypoxia-activated cytotoxin (tirapazamine) is in clinical trial, no drug that directly targets hypoxic tumor cells is in clinical use. HIF-1 is a hypoxia induced transcription factor that activates expression of genes that are required for tumor cells to adapt and survive in a hypoxic environment. Hypoxic activation of HIF-1 leads to increased transcription from the reporter gene and results in increased luciferase activity. www.usm.edu /niust/obcrproject1.htm   (509 words)

Improvement of tumor response by manipulation of tumor oxygenation during photodynamic therapy Photochemistry and ...   (Site not responding. Last check: 2007-10-25) C3H mice with transplanted mammary carcinoma tumors were injected with 12.5 mg/kg Photofrin and irradiated with 630 nm laser light 24 h later. Tumor oxygenation was manipulated by subjecting the animals to 3 atp (atmospheric pressure) hyperbaric oxygen or normobaric oxygen during PDT light irradiation. To explore the effect of hyperoxygenation on tumor oxygenation, tumor partial oxygen pressure was measured with microelectrodes positioned in preexisting hypoxic regions before and during the PDT. www.findarticles.com /p/articles/mi_qa3931/is_200208/ai_n9094016   (909 words)

HER-2/neu Overexpression Increases the Viable Hypoxic Cell Population within Solid Tumors without Causing Changes in ... tumor viability and a significant increase in the population tumor: hypoxic tumor cells are residing at the border of viable and necrotic tissue; viable tumor tissue exhibits well organized, confluent structure, and necrotic tumor tissue located outside hypoxic areas has distorted and loose structure. of tumor microvessel density, is summarized in Fig. mcr.aacrjournals.org /cgi/content/full/2/11/606   (6875 words)

Replication and Cytopathic Effect of Oncolytic Vesicular Stomatitis Virus in Hypoxic Tumor Cells In Vitro and In Vivo ... in antiviral responses in the tumor cells (6, 36, 37). VSV replication in hypoxic tumor tissue in vivo. For panels A to C and G, C6 tumors were intratumorally treated with VSV and the tumor was labeled with EF-5 in a separate injection 24 h later (see Materials and Methods). jvi.asm.org /cgi/content/full/78/17/8960   (6448 words)

About AQ4N - Novacea.com It is widely accepted by researchers that hypoxic fractions of tumors are less responsive to radiotherapy and chemotherapy. This lower response can be attributed to the fact that hypoxic cells are less active than oxic cells; they are not replicating and are thus less vulnerable to cell killing through DNA damage. Because AQ4N targets hypoxic tumor regions (which are resistant to radiation and chemotherapy), it may be less likely to produce systemic toxicities. www.novacea.com /420.asp   (564 words)

Tumor hypoxia - Wikipedia, the free encyclopedia Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. They are relevant in the study of radiation therapy as they can be made more susceptible to treatment by increasing the amount of oxygen in them. Study of tumors in such conditions was pioneered by Dr L. Gray. en.wikipedia.org /wiki/Hypoxic_tumor   (83 words)

CiteULike: Preferential activation of mitomycin C to cytotoxic metabolites by hypoxic tumor cells.   (Site not responding. Last check: 2007-10-25) CiteULike: Preferential activation of mitomycin C to cytotoxic metabolites by hypoxic tumor cells. Preferential activation of mitomycin C to cytotoxic metabolites by hypoxic tumor cells. Mitomycin C, a bioreductive alkylating agent with clinical utility against several human tumors, was found to be selectively toxic at a relatively low concentration (1.5 micro M) to EMT6 tumor cells made chronically hypoxic by preincubation in 95% N2-5% CO2 for 4 hr prior to drug exposure. www.citeulike.org /user/ecattell/article/1335086   (529 words)

MECHANISMS OF TUMOR RADIORESISTANCE Hypoxic tumor cells are 2.5 to 3.0 times more resistant to killing by ionizing radiation than are aerobic cells. Recent microelectrode studies with human tumors of the cervix and the head and neck indicate that low oxygen levels in solid tumors strongly predict for treatment failure after radiation and other therapies. Hypoxic microenvironments in tumors were found also to promote mutation and metastases and to select for aggressive tumor phenotypes. www.fccc.edu /research/reports/current/chapman.html   (1679 words)

University of Pennsylvania Health System: News and Periodicals: Penn Researchers Create Drug to Help Target Attack on ...   (Site not responding. Last check: 2007-10-25) The drug, EF5, permits doctors to effectively determine the oxygen content of a tumor -- which subsequently dictates the appropriate course of treatment to be followed. Cancer clinicians have long known that hypoxic tumors -- which thrive in oxygen-starved environments -- are much more resistant to radiation and chemotherapy than their non-hypoxic cousins. In the trial, a second method of measuring hypoxia is also employed: A thin needle electrode is inserted into the tumor to measure the oxygen content. www.uphs.upenn.edu /news/News_Releases/feb98/tumor.shtml   (514 words)

Drug Destroys Only Oxygen-Starved Cells Within Tumors And the higher the percentage of hypoxic cells in a tumor, the worse the prognosis for the patient. Indeed, they are only found in tumors, due to the poorly formed chaotic vessels which develop inadequately in the tumor to meet the needs of the fast growing tumor cells. Standard therapies primarily target better oxygenated cells, leaving the hypoxic cells to repopulate the tumor; for complete tumor control, it may be essential to kill this more malignant subpopulation. unisci.com /stories/20013/0719012.htm   (747 words)

Review: Implications of In Vitro Research on the Effect of Radiotherapy and Chemotherapy Under Hypoxic Conditions -- ... in the oxygenation status of acutely hypoxic tumor cells [165]. Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer. Hypoxia in tumors: A paradigm for the approach to biochemical and physiologic heterogeneity. theoncologist.alphamedpress.org /cgi/content/full/12/6/690   (7075 words)

Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues -- Murdoch ...   (Site not responding. Last check: 2007-10-25) (A) Hypoxic areas (arrow), visualized by immunolabeling of the reductively activated hypoxic-specific marker pimonidazole (red), are observed at a distance from the disorganized blood vessels (BV). in the supernatants of hypoxic tumor cells in vitro. Endothelin-2 is a macrophage chemoattractant: implications for macrophage distribution in tumors. www.bloodjournal.org /cgi/content/full/104/8/2224   (6675 words)

Endothelin-2 Is a Hypoxia-induced Autocrine Survival Factor for Breast Tumor Cells -- Grimshaw et al. 1 (14): 1273 -- ... An antibody control was probed with an irrelevant antibody (rabbit polyclonal against gastrin, which is not expressed in the breast or tumors) and a serum control-used rabbit serum instead of the primary antibody. Positive staining of ET could be found in the tumor samples (c-neu-positive 5 of 5 and c-neu-negative 5 of 5) but not in normal breast tissue (0 of 5) or benign fibroadenoma tissue (0 of 5). hypoxic survival of HTH-K cells using antagonists of the ET receptors. mct.aacrjournals.org /cgi/content/full/1/14/1273   (5405 words)

Cancer Chemotherapy: Online Reference For Health Concerns The goal of chemotherapy is to shrink primary tumors, slow the tumor growth, and kill cancer cells that may have spread (metastasized) to other parts of the body from the original, primary tumor. A partial remission is defined as 50% or greater reduction in the measurable parameters of tumor growth as may be found on physical examination, radiologic study, or by biomarker levels from a blood or urine test. Since cancer cells thrive in a hypoxic environment, the cancer patient's hematocrit and hemoglobin should be maintained in the upper one-third of normal range prior to the initiation of chemotherapy. www.lef.org /protocols/prtcl-024.shtml   (2568 words)

1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine: An anticancer agent targeting ... of viable malignant cells in hypoxic regions of the tumor. Surviving fractions were calculated by using the plating efficiencies of aerobic and hypoxic vehicle-treated controls within the same experiment. Surviving fractions were calculated by using the plating efficiencies of aerobic and hypoxic vehicle-treated controls. www.pnas.org /cgi/content/full/102/26/9282   (3862 words)

Marking Hypoxia in Rat Prostate Carcinomas with {beta}-D-[125I]Azomycin Galactopyranoside and [99mTc]HL-91: Correlation ... tumors in both rodents and humans was recently reviewed (15). Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Evidence for acutely hypoxic cells in mouse tumors and a possible mechanism for reoxygenation. jnm.snmjournals.org /cgi/content/full/42/2/337   (3749 words)

Macrophage Responses to Hypoxia: Implications for Tumor Progression and Anti-Cancer Therapies -- Lewis and Murdoch 167 ... Tumor hypoxia was visualized by injecting mice bearing 4T1 mammary tumors or breast cancer patients with the hypoxic cell marker pimonidazole (PIMO) before surgical removal of tumors. PIMO retained by hypoxic cells in tumor sections was then detected using a rabbit anti-PIMO antibody (red staining, arrows in B and D). Macrophage functions in a hypoxic tumor area: involvement in tumor growth, invasion, metastasis, and angiogenesis. ajp.amjpathol.org /cgi/content/full/167/3/627   (5613 words)

Research at the Faculty of Medicine Cell cycle regulation is one of the main topics in modern tumor biolog............ Tumor cells are characterized by acquired genetic changes, many of whi............ The capacity of tumor cells to induce angiogenesis is a prerequisite f............ www.research.med.lu.se   (5997 words)

Candidate Genes for the Hypoxic Tumor Phenotype -- Koong et al. 60 (4): 883 -- Cancer Research from a punch biopsy derived from a hypopharyngeal tumor. In addition, the induction of each gene by the hypoxic mimetic agent DFO (6 h) is also included to further support the hypoxia-inducibility of each gene. the serum of oxic tumors with hypoxic tumors. cancerres.aacrjournals.org /cgi/content/full/60/4/883   (5186 words)

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