Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type C retroviruses are endogenous in most vertebrate species. These viruses generally are of low pathogenicity in their natural hosts. Variants that contain cell-derived transforming genes have been isolated infrequently in the past upon continued passage in vivo. We report here a procedure that allows the isolation of new mouse leukemia-, sarcoma-, and carcinoma-inducing type C viruses entirely in cell culture. The viruses generated after passage in chemically transformed mouse cells and selectron in epithelial mink lung cells produced pulmonary adenomas and adenocarcinomas and also ovarian carcinomas. Viruses with cell-transforming capacity, as determined by their ability to induce normal murine or mink cells to form progressively growing colonies in soft agar, appeared only transiently (2-4 days) after acute infection of "spontaneously" or chemically transformed mouse cells by nontransforming helper viruses. These transiently appearing transforming viruses can be "captured" by selecting the cells that respond to their newly acquired growth-stimulating ability. This system may lend itself to the systematic isolation of tissue-specific transforming functions from any cell that can be efficiently infected by retroviruses.
 ...
PMID:Generation of oncogenic mouse type C viruses: in vitro selection of carcinoma-inducing variants. 624 70

To specify the mechanism whereby inoculation of sarcoma viruses protects against leukemia development by leukoviruses, several experiments were performed using Friend virus complex (FVC) and MSV-F, a sarcoma virus pseudotype prepared in vitro with FVC as source of the helper component. The sarcomatous lesions induced by MSV-F were self-limited, irrespective of dose and route of inoculation and protected against the progressive, lethal erythroleukemia induced fy FVC. The sera of MSV-F primed mice had high FVC-neutralizing titers, Out of 3 properties titered in FVC, immunogenicity, XC-syncytium-forming activity and lethality, the frmer two were retained at high titers in MSV-F, while lethality was almost entirely lost: the dose-range between lethal immunizing dilutions was 2-3 logs broader for MSV-F than for FVC. It is postulated that the lethal, early erythroleukemia inducing component (Spleen Focus Forrming Virus) is rapidly lost from FVC upon in vitro propagation. The rescued MSV-F would carry a hightitered, immunogenic and Xc-syncytium forming component (Lymphatic Leukemia Virus), thus behaving as an immunogenic virus of limited pathogenicity.
 ...
PMID:Immunity to Friend virus complex: analysis of protection with a sarcoma virus pseudotype. 625 97

The DNase I sensitivity of chromosomal DNA regions carrying integrated proviral genomes of Moloney (M-MuLV) and AKR Murine Leukemia Virus (AKR-MuLV), and the cellular homologue of the mos-gene (c-mos) of Moloney Sarcoma Virus (MSV) were studied in tumor tissues of leukemic mice. The genetically transmitted sequences of M-MuLV, AKR-MuLV, and the c-mos gene are all in DNase I resistant chromatin conformations in M-MuLV-induced tumors. Each M-MuLV-induced tumor contained at least one somatically acquired integrated recombinant MuLV genome that displayed two main characteristic features of active chromatin: a) a configuration hypersensitive to DNase I, and b) extensive hypomethylation. DNase I hypersensitive sites were mapped at the junction of cellular sequences and the 5'-viral large terminal repeat (LTR). Expression of a recombinant MuLV seems therefore to be a necessary feature to maintain the transformed state.
 ...
PMID:Moloney murine leukemia virus-induced tumors: recombinant proviruses in active chromatin regions. 627 22

4'-epi-doxorubicin (4'-epi-DX) is a new anthracycline antibiotic. It differs from doxorubicin (DX) by the epimerization of the OH group in position 4' of the aminosugar moiety, and was synthesized in an effort to find agents with a superior therapeutic index to the parent compound doxorubicin (DX). 4'-epi-doxorubicin binds to DNA and inhibits nucleic acid synthesis and function. The antitumor activity of 4'-epi-DX in several experimental tumors (Leukemias L 1210, P 388, Gross Leukemia, Sarcoma 180 ascitic and solid, C3H/HE mammary carcinoma) is similar to that of DX. However, 4'-epi-doxorubicin has greater antitumor activity than doxorubicin in Lewis lung carcinoma, MS-2 sarcoma lung metastasis, and human melanoma in athymic mice. In chronic toxicity studies there were no qualitative differences between 4'-epi-DX and DX; quantitatively, however, 4'-epi-DX was less toxic. In different experimental models 4'-epi-DX has been shown to be less cardiotoxic than its parent compound. In chronic toxicity studies in the rabbit, histopathologic findings revealed the same pattern of cardiotoxicity for both drugs but less marked with 4'-epi-DX. Distribution studies in mice with tumors showed a lower concentration of 4'-epi-DX in the heart, spleen and kidneys; the hepatobiliary metabolism and excretion of 4'-epi-DX investigated in the rat, indicated that the new analogue was more extensively metabolized than the parent compound. Pharmacokinetics of 4'-epi-DX in humans showed a multiexponential decrease of plasma levels; the same pattern was observed for the metabolite 13-OH epidoxorubicinol but with lower concentrations than the unchanged drug. A high plasma clearance (0.9-1.41/min), a terminal half-life of about 30-40 hr and a large volume of distribution were the main pharmacokinetic characteristics of 4'-epi-DX. A reduction of the dose appears to be appropriate in patients with liver function impairment. Phase II studies with 4'-epi-DX have indicated that the drug produces a pattern of acute toxicity, including acute cardiac toxicity, qualitatively similar to that of DX at identical doses but quantitatively lower, with particular regard to leukopenia and gastrointestinal toxicity. The range of single active doses is between 60 and 90 mg/m2, the most frequently employed doses schedules being 75 or 90 mg/m2 i.v. every 3 weeks. 4'-epi-DX has shown activity in a variety of tumors such as breast carcinoma, soft tissues sarcomas, NH lymphomas, leukemias, ovarian cancer and gastric cancer. Preliminary evidence of activity has been found in melanoma, rectal cancer and pancreatic cancer suggesting a broad spectrum of activity. As to chronic cardiac toxicity up to now only 2 mild to moderate and reversible CHF have been observed at doses of 1120 and 1235 mg/m2 in about 700 treated patients. Specific and comparative studies are in progress: preliminary findings from a randomized comparison of 4'-epi-DX vs DX in breast cancer indicated that 4'-epi-DX may have a lower cumulative cardiotoxicity.
 ...
PMID:4'-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data. 634 72

Cancer mortality among children in the United States, 1950 through 1979, as evaluated by death certificate diagnoses, revealed dramatic declines primarily in the second half of the 30-year interval. The numbers of deaths of persons younger than 15 years, 1965 through 1979, as compared with the number expected at 1950 rates, fell 50% for leukemia, 32% for non-Hodgkin's lymphoma, 80% for Hodgkin's disease, 50% for bone sarcoma, 68% for kidney cancer, and 31% for all other cancer. There were 17,411 fewer deaths from childhood cancer from 1965 through 1979 than expected at the 1950 rate. Leukemia mortality declined by 8,073 deaths and kidney tumor mortality by 2,393. In data subsequently received for 1980, the decline in rates persisted for leukemia and non-Hodgkin's lymphoma, but the rates for the other four cancer categories seem to have reached a plateau. The reduction in mortality is attributed to improved therapy.
 ...
PMID:Decline in US childhood cancer mortality. 1950 through 1980. 636 67

An unusual case of meningeal granulocytic sarcoma without evidence of Leukemia is presented. The patient, a 40 year old female, presented with a chronic subdural haematoma. Three months later a large meningeal tumor was discovered adjacent to the previous haematoma and was found to be a granulocytic sarcoma by the use of electron microscopy. The tumor was treated by surgical excision followed by radiotherapy and chemotherapy. The patient remains free of symptoms and without evidence of leukemia in the peripheral blood or bone marrow 9 months after the diagnosis was established. The ultrastructural findings in the tumor and diagnostic difficulties often encountered are emphasized.
 ...
PMID:Meningeal granulocytic sarcoma without evidence of leukemia. Light and ultrastructural study of one case. 694 46

The major focus of cancer immunology has shifted away from arguments about the validity of the immunosurveillance theory of cancer to the more basic question of tumor-specific antigens. Despite vast effort aimed at demonstrating such antigens, their existence in the generality of cancer remains unproven. Serological analysis of three tumor types, mouse leukemia, mouse sarcoma, and human malignant melanoma, has received most attention, and a rudimentary classification of the surface antigens expressed by these tumors has begun to emerge. The prime candidates for antigens that can be considered tumor specific are the few instances of Class 1 antigens that have now been serologically defined on mouse and human tumors. These antigens show an absolute restriction to individual tumors, not being demonstrable on any other normal or malignant cell type. Biochemical and genetic characterization of Class 1 antigens represents an essential next step in evaluating the significance of these antigens. The surprising features of the Thymus Leukemia (TL) antigens of the mouse provide insight into the genetic origin of another key class of tumor antigens, in this case antigens with characteristic properties of both differentiation antigens and tumor-specific antigens. In normal mice, TL antigens are restricted to cells in the thymus, and strains differ with regard to expression versus nonexpression of TL antigens. Genetic information for TL is universal in the mouse, however, as leukemias developing in mice that normally lack TL are found to express TL. What is clear from the past two decades of research in cancer immunology is that a far more detailed knowledge of surface antigens of tumor cells will be necessary before we can begin to assess the possibility of immunological control of cancer.
 ...
PMID:Cancer immunology: the search for specificity--G. H. A. Clowes Memorial lecture. 700 32

Despite their generally favorable mortality experience, general occupational surveys of farmers suggest they have elevated risks of cancer of the lymphatic and hematopoietic systems, stomach, prostate, brain, and skin. Since farmers often serve in the role of mechanic, carpenter, welder, pesticide applicator, and veterinarian, they may be exposed to many potentially hazardous substances. The types and levels of exposures have been discussed by others earlier in the program. The evidence is strongest for the association between farming and risk of leukemia. However, the specific leukemogenic agent or agents have yet to be identified. Leukemia excesses among poultrymen and dairy farmers suggest involvement of zoonotic viruses, while associations with crop production is more indicative of pesticide usage. The associations regarding other cancers (i.e., Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, soft-tissue sarcoma, and cancers of the stomach, brain, and prostate) are even less clear. However, the Swedish reports of high risk of soft-tissue sarcomas and lymphomas among persons exposed to herbicides is particularly disconcerting and underscores the urgent need for similar epidemiologic studies in the U.S. Several case-control interview studies are underway that should help clarify the role of agricultural factors in the origin of various cancers. NCI is sponsoring studies of leukemia and non-Hodgkin's lymphoma among men from Minnesota and Iowa. Detailed information on farm practices and pesticide usage is being gathered. A study of soft-tissue sarcoma, Hodgkin's disease, and non-hodgkin's lymphoma also has just been initiated. This investigation is located in Kansas, a major wheat producing area. A wheat producing area was selected because herbicides are more heavily used on this crop than insecticides. The major objective of this project is to evaluate the role of herbicides in the origin of these cancers. A case-control study of brain cancer has also recently been initiated. Although this study focuses on contact with petrochemicals, a complete work history will be obtained and would note any farm experience. These data may help clarify the reported association between brain cancer and farming.
 ...
PMID:Cancer risks associated with agriculture: epidemiologic evidence. 715 Feb 8

In sarcomagenesis in rats infected neonatally with feline sarcoma virus (ST-FeSV), v-fes product (P85) was previously shown by us to be a predictive and preventive determinant. In order to explore the part played by P85 in tumor suppression, DNA was extracted from precancerous granulomas and from slow or rapid growing sarcomas induced by neonatal injection of the virus. The v-fes signal from extracted DNA was analyzed by PCR-SSCP. The prototype v-fes gene signal was detected in most lesions and found to be generally amplified in rapid growing sarcomas and in some granulomas. Several v-fes homologs showing varying mobilities in gel were seen in most sarcomas and some granulomas with or without the prototype v-fes signal. In slow growing sarcomas and granulomas induced in hosts that were immunized with ST-FeSV induced syngeneic sarcoma and proved to carry IgG antibody to P85, the prototype v-fes gene was found to be down-regulated and v-fes homologs were found to be reduced in number or eliminated. These results suggest that the development of v-fes mutations is associated with the growth potential of cells carrying the v-fes gene, and that host immunity to v-onc product influences the development of virogene rearrangements and results in slow and suppressed growth of tumors caused by neonatal infection with retrovirus.
Leukemia 1995 Oct
PMID:V-onc mutation associated with host cell growth in retroviral tumors. 747 23

A fatal systemic proliferation of malignant histiocytes resembling human malignant histiocytosis was induced in susceptible mice following infection with the murine retrovirus malignant histiocytosis sarcoma virus (MHSV). It is shown that MHSV additionally caused profound alterations of erythropoiesis, granulocytopoiesis and thrombocytopoiesis, and in the hemopoietic stem cell compartment. In the erythroid lineage, MHSV induced a normocytic peripheral anemia, which was paralleled by an unphysiologic, multifocal clonal expansion of erythroid blasts in the spleen. These cells were not transformed and appeared to have a maturation defect since blood reticulocytes did not increase above control values. Moreover, MHSV exerted cytopathic effects on neutrophilic granulocytes and megakaryocytes, since their numbers transiently decreased in the spleen, and agranulocytosis and thrombocytopenia was observed in the blood. Nonetheless, regeneration was found in both lineages at later stages of the infection, which was accompanied by a terminal granulocytosis. The number of lineage-committed and multipotential colony-forming cells in the CFU-S assay increased transiently, but decreased to very low levels in the final stages of the disease. Thus, the studies demonstrate that the same etiologic agent, MHSV, had different effects on hemopoietic cells, which included malignant transformation, hyperproliferative and cytopathic effects.
Leukemia 1995 Apr
PMID:Perturbations of multiple hemopoietic lineages in retrovirus-induced murine malignant histiocytosis. 772 6


<< Previous 1 2 3 4 5 6 7 8 Next >>