Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article discusses the role of transcription factors in vascular endothelial growth factor (VEGF) gene expression. Angiogenesis is a complex and multilevel process of new capillary formation on the basis of already existing blood vessels. Physiologically, it is a very strictly regulated process, which results in a balance between stimulatory (angiogenic) and inhibitory (angiostatic) factors to control the correct development of blood vessels. There are many very well characterized angiogenic and angiostatic factors that can modulate VEGF expression. Some of them (e.g. HIF-1, AP-1, and Sp-1) are transcription factors, proteins that bind to the VEGF promoter to initiate and activate the transcription of a gene directly. Others, like nitric oxide or cytokines, are agents that stimulate the transcription factors through different cellular signaling pathways. There are also oncogenes (V-SRC, bcl-2) and tumor suppressor genes (VHL), the mutations of which lead indirectly to increased transcription of the VEGF gene.
Med Sci Monit 2004 Apr
PMID:Transcription factors having impact on vascular endothelial growth factor (VEGF) gene expression in angiogenesis. 1503 60

Serial analysis of gene expression (SAGE) is a powerful tool that allows digital analysis of overall gene expression patterns. SAGE provides quantitative and comprehensive expression profiling in a given cell population. Because SAGE does not require a preexisting clone, it can be used to identify and quantitate new as well as known genes. It works by isolating short fragments of genetic information from the genes expressed in the cell being studied. These short sequences, called SAGE tags, are linked together for efficient sequencing. SAGE is particularly well suited for organisms whose genome is not completely sequenced, because it does not require a hybridization probe for each transcript and allows new genes to be discovered. New modifications of SAGE now permit the analysis of gene expression in cell sub-populations or micro-anatomic structures, providing access to unexplored transcriptomes of normal and disease biology. Data derived using the SAGE technology have been used to identify tumor markers for a variety of cancers, including gastrointestinal cancer, lung and thyroid cancer, breast and ovarian cancer, neuroblastoma and glioblastoma, prostate cancer, and renal cell carcinoma. In this review we present an outline of the method and updated information on the applications of SAGE technology to various cancers.
Med Sci Monit 2004 Jun
PMID:Serial analysis of gene expression (SAGE): application in cancer research. 1517 83

The goal of chemotherapy is the elimination of tumor cells from the host. This is achieved by the use of therapeutic agents that are often more harmful to normal tissues than to the targeted tumor. Many chemotherapeutic agents are designed to damage cell replication machinery either directly at the level of DNA or indirectly, by inhibiting enzymes involved with DNA repair and synthesis. Novel therapeutic agents that exert their effects at signal transduction pathways have advanced chemotherapy; however, a role for the classic chemotherapeutic agents remains. These classic agents are associated with tumor cell resistance, toxicity, and occasionally secondary neoplasia. Current practices for the dosing of therapeutic agents rely on height and body surface measurements or drug monitoring and Bayesian adaptive control. Pharmacogenetics is emerging as an alternate approach to managing chemotherapy that may prevent undertreatment while avoiding overtreatment and associated toxicities. By determining the polymorphic genetic makeup of the host and, in some instances, the altered genetic expression of the tumor, chemotherapy can be tailored for interindividual response and toxicity avoidance. Chemotherapy is particularly applicable to the pharmacogenetic approach to tailored therapy for a number of reasons. The margin of safety is low with chemotherapeutic agents. Some drugs require biotransformation for activation. Drug activation correlates with toxicity. The pathways of drug clearance or inactivation exhibit polymorphic differences. Interindividual, race-specific, and age-related responses to chemotherapeutic agents are common. Last, drug resistance can be inherent to the tumor as a result of the suppression of apoptosis. Variations in response and toxicity to a specific drug can be caused by alterations in drug-metabolizing enzymes or receptor expression. These effects can be classed as pharmacokinetic and pharmacogenetic differences. Some of the genes known to display polymorphic differences include FLT3 receptor tyrosine kinase, FCG3RA IgG FC receptor, thymidylate synthase, methylenetetrahydrofolate reductase, thiopurine S-methyltransferase, dihydropyrimidine dehydrogenase, aldehyde dehydrogenase, glutathione S-transferase, uridine diphosphate glyuronosyl transferases, N-acetyl transferases, cytochrome P450, and the DNA repair enzymes XPD and XRCC1. To be successful a pharmacogenetic approach to individualized chemotherapy must selectively take advantage of a determination of direct enzyme activity, gene expression, and genotype.
Ther Drug Monit 2004 Apr
PMID:Pharmacogenetics in cancer chemotherapy: balancing toxicity and response. 1522 71

PTEN is a dual-specificity phosphatase with both protein phosphatase and lipid phosphatase activity. PTEN is the first phosphatase identified as a tumor suppressor. Not since the discovery of p53 has a tumor suppressor generated such interest. Initial studies performed on cancer cell lines suggested that PTEN may be responsible for almost all types of cancer, both solid tumors and hematological malignancies. Biallelic deletion of PTEN has been associated with advanced stage tumors or metastatic disease. PTEN has been shown to play a pivotal role in apoptosis, cell cycle arrest, and possibly cell migration. Emerging data suggest that this may be an oversimplification of PTEN's role, and that PTEN may be haploinsufficient for tumor progression and may play important roles in other cellular functions such as angiogenesis and MAP kinase signaling.
Med Sci Monit 2004 Oct
PMID:PTEN regulatory functions in tumor suppression and cell biology. 1544 14

Among the many potential antiangiogenic agents now in various stages of preclinical or clinical study, genistein (GEN) has generated wide interest being because of its natural origin (soybeans) and epidemiological studies showing the cancer chemopreventive effects of soybean consumption. In this paper the in vivo effects of GEN applied either alone or together with cyclophosphamide on the growth of mouse transplantable mammary carcinoma (16/C) transplanted either orthotopically or ectopically is presented. The growth of 16/C mouse mammary cancer transplanted subcutaneously (s.c.) or into the mammary gland (orthotopically-orth.) was stimulated by GEN administered from day 4 after tumor cell inoculation. Such stimulation was not observed when the treatment with GEN was started at day 12 after cell inoculation. Stimulation of tumor growth by GEN was markedly higher in mice transplantedorth. than in those transplanted s.c.. However, GEN did not affect the expression of estrogen (ER)and progesterone receptors (PgR) in the orthotopic model of 16/C cancer. In the case of subcutaneously growing tumors, treatment with GEN lowered (2-fold) the expression of both ER and PgR. In the interpretation of these results, the pleiotropic (including hormonal and antiproliferative), sometimes opposing effects of genistein in vivo should be considered. It seems rather reasonable to exclude breast and, perhaps, other hormone-dependent cancers from the treatment and chemoprevention with soy-derived phytoestrogens until its mechanism(s) of action on various cancer cells is completely understood.
Med Sci Monit 2004 Nov
PMID:Genistein alone or combined with cyclophosphamide may stimulate 16/C transplantable mouse mammary cancer growth. 1550 46

Some cytological aspects of rat mammary cancer therapy with soluble tumor-associated antigens (sTAA- p66 and p51) and the anticancer drug cyclophosphamide (CPA) are analyzed. Vaccination with sTAA results in a significant increase in the areas related to the production of T and B cells in the white pulp (germinal center and PALS) and in the marginal zone of the spleen. sTAA stimulate the production of CD8+ lymphocytes inside the tumors and in bone marrow, and of CD8+ thymocytes in the medulla of the thymus. Treatment of rats with CPA decreases the activity of lymph cells in tumors, especially of CD4+ lymphocytes. In the spleen, CPA decreases the size of areas related to the production of B and T cells. In the bone marrow, CPA affects the process of myelogenesis and causes significant substitution of cellular components with fatty tissue. The combined treatment with CPA and sTAA increases the number of lymph cells and the apoptotic index in tumors, and restored the rate of B cells producing in the spleen. Similar effect was observed in lymph nodes with accumulation of B lymphocytes in the primary and secondary follicles, and of T lymphocytes in the paracortical zone. In the thymus, CPA alone or in combination with sTAA repairs the inhibitor effect of a carcinogen on synthesis of CD4+ and CD8+ thymocytes. In combined using with CPA, sTAA activate the B- and T-lymphocyte production in the host's immune system and decrease the toxic side-effects of a drug.
Med Sci Monit 2005 May
PMID:Cytological aspects of rat mammary cancer therapy with soluble tumor-associated antigens and anticancer drugs. 1587 8

Cachexia, or the loss of skeletal muscle, adipose tissue and immunological competence, is a common systemic condition in advanced cases of cancer, and is a frequent cause of death. There have been many reports that small peptides isolated from tumors induce systemic effects correlated with cachexia upon injection into mice or addition to cell cultures. Only recently has evidence been presented for the origin of these peptides from the large increase in proteolytic enzymes found in tumors. Additional evidence is presented here for a major role of tumor peptides in producing effects associated with cachexia. Such peptides of low molecular weight were found to produce lipolysis in adipose tissue. Fibrinogen degradation products from the plasma of cancer patients and other chronic diseases suppress activation of the immune response. Some proteases of the cathepsin class occur in high concentration at the surface of transformed cells where the pH is low enough to allow digestion of pericellular proteins; other cathepsins elevated in tumors are highly active at physiological pH. Cathepsin L is the major excreted protein of cultured cells transformed by viruses or chemicals and is likely to form toxic peptides by digestion of extracellular proteins. Even normal liver and skeletal muscle of some cancer patients and tumor-bearing animals exhibit significant increases in cathepsins and components of the ubiquitin-proteasesome pathway which would add to circulating peptides. These observations argue for a central role of multiple proteases and their proteolytic products in producing the debilitating systemic effects of cancer.
Med Sci Monit 2005 Jul
PMID:Systemic effects of cancer: role of multiple proteases and their toxic peptide products. 1599 Jun 98

Over the past 40 years, hyperbaric oxygen (HBO2) therapy has been recommended and used in a wide variety of medical conditions. In the 1950s, HBO2 was first used as a treatment, in addition to radiation, for head and neck cancers and cervical cancer. Many studies have been conducted to investigate possible therapeutic effects HBO2 as part of cancer management. Evidences showed that HBO2 improved tumor oxygenation, and treatment with HBO2 during irradiation has been shown to improve the radiation response of many solid tumors. It was used for delayed radiation injuries for soft tissue and bony injuries, for symptomatic radiation reactions of the urinary bladder and the bowel, for laryngeal radionecrosis, for radiation-induced optic neuropathy, for radiation-induced proctitis and for radiation-induced necrosis of the brain. HBO2 also increases sensitivity to chemotherapy. A significant improvement in tumor response was obtained when photodynamic therapy (PDT) was delivered during hyperoxygenation. These studies were extensively reviewed and rational scientific basis for further investigations was discussed. The possibility of combining HBO2, PDT and photosensitizers to overcome primary and secondary carcinoma deserve extensive laboratory and clinical research works. HBO2 is a relatively benign with few contraindications, even for active cancer patients.
Med Sci Monit 2005 Sep
PMID:Hyperbaric oxygen and malignancies: a potential role in radiotherapy, chemotherapy, tumor surgery and phototherapy. 1612 74

The liver is continuously exposed to a large antigenic load that includes pathogens, toxins, tumor cells and dietary antigens. Amongst the hepatitis viruses, only hepatitis B virus (HBV) and hepatitis C virus (HCV) cause chronic hepatitis, which can progress to cirrhosis and hepatocellular carcinoma. Of the different antiviral defense systems employed by the tissue, apoptosis significantly contributes to the prevention of viral replication, dissemination, and persistence. Loss of tolerance to the liver autoantigens may result in autoimmune hepatitis (AIH). This review outlines the recent findings that highlight the role and mechanisms of apoptotic processes in the course of liver diseases. Among factors that contribute to liver pathology, we discuss the role of tumor necrosis factor (TNF)-alpha, HBx, ds-PKR, TRAIL, FasL, and IL-1alpha. Since TNF and FasL-induced hepatocyte apoptosis is implicated in a wide range of liver diseases, including viral hepatitis, alcoholic hepatitis, ischemia/reperfusion liver injury, and fulminant hepatic failure, these items will be discussed in greater detail in this review. We also highlight some recent discoveries that pave the way for the development of new therapeutic strategies by protecting hepatocytes (for example by employing Bcl-2, Bcl-XL or A1/Bfl-1, IAPs, or synthetic caspase inhibitors), or by the induction of apoptosis in stellate cells. The assessment of the severity of liver disease, as well as monitoring of patients with chronic liver disease, remains a major challenge in clinical hepatology practice. Therefore, a separate chapter is devoted to a novel cytochrome c-based method useful for the diagnosis and monitoring of fulminant hepatitis.
Med Sci Monit 2005 Nov
PMID:Apoptosis in liver diseases--detection and therapeutic applications. 1625 9

This study was designed to report the pharmacokinetic behavior of Rituximab in patients affected with different diseases and treated with different schedules of administration. A low tumor burden was a common feature of all patients (N=48) included in our study, whereas the timing of Rituximab administration varied from weekly (groups 1, 2, 3) to monthly (group 4). Group 1 included patients with follicular lymphoma treated with 4 weekly doses of Rituximab after first-line chemotherapy with CHOP. At the start of Rituximab, patients were in partial or complete clinical response but showed persistence of disease at molecular level (bcl-2-positive) in bone marrow and/or peripheral blood. Patients in group 2 had autoimmune disorders and Rituximab was given to act on B-cells, interfering with their production of autoantibodies. In patients with amyloidosis (group 3), Rituximab was given to kill progenitor B-cells of the small clone terminating in amyloid-producing plasma cells. In groups 2 and 3, the target of monoclonal antibody was a population of small B cells, which make an intrinsic feature of the diseases. Group 4 included patients with relapsed or refractory follicular and mantle cell lymphoma who underwent a salvage program of immunochemotherapy, purging in vivo and autotransplant: the first of the six planned doses of Rituximab was administered after a debulking phase with a third-generation regimen, such as VACOP-B. An enzyme-linked immunoassay (ELISA) developed and validated in our laboratory was used for the pharmacokinetic study. Rituximab disposition was characterized by a 2-exponential decay, with a long elimination half-life of approximately 3 weeks (range, 248-859 hours). The total systemic clearance ranged between 3.1 and 11.9 mL/hr/m. After 4 weekly infusions, Rituximab concentration was approximately 2.5 microg/mL, which is approximately 85% of the steady-state level. Steady-state plasma concentrations of Rituximab were reached after 6 to 8 weekly infusions. The adopted pharmacokinetic model (2-compartment open model) seems to provide the best fit of Rituximab disposition both during and after treatment, even when different schedules of drug administration are used. Because several studies reported an association between response and serum Rituximab concentrations, a treatment based on a pharmacokinetic model may be useful for predicting the desired drug concentration.
Ther Drug Monit 2005 Dec
PMID:Pharmacokinetic behavior of rituximab: a study of different schedules of administration for heterogeneous clinical settings. 1630 56


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