Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ru 41.740 (Biostim) is an immunostimulating drug of microbial origin which may stimulate human mononuclear blood cells (mainly monocytes) to release soluble factors which inhibit replication of several tumor cell lines in vitro. Since this effect may be of clinical importance in the treatment of cancer a number of tests have been conducted in order to find methods to augment this secretion. In vitro tests suggested that this non-specific antitumor activity of Biostim may not be enhanced by concomitant treatment of patients with inhibitors of cyclo-oxygenase and lipoxygenases or by interferons alpha, beta, gamma or the hemopoietic growth factors GM-CSF and G-CSF.
 ...
PMID:Ru 41.740 triggers human mononuclear blood cells to release tumor growth inhibitory factors in vitro. 137 44

Anemia and neutropenia are common complications of HIV infection. Antiretroviral therapy with zidovudine exacerbates bone marrow suppression by inhibiting proliferation of blood cell progenitor cells. In addition, treatment for opportunistic infections or malignancies can involve the use of myelosuppressive drugs. As a consequence, severe anemia and neutropenia can result, thereby limiting the utilization of antiretroviral drugs. Since antiretroviral therapy can increase survival, drugs that ameliorate myelosuppression are important adjuncts in the treatment of HIV-infected patients. Three hematopoietic growth factors are effective in the treatment of anemia or neutropenia. In four placebo-controlled trials, erythropoietin (EPO) at doses up to 600 U/kg/wk decreased mean transfusion requirements by 37%, increased mean hematocrit by 4.5% and corrected anemia in the majority of patients receiving zidovudine over a 12-week period. In a separate study, granulocyte colony-stimulating factor (G-CSF) corrected leukopenia and isolated neutrophil defects in 22 patients with AIDS without altering HIV expression. When erythropoietin was added to the regimen, combined G-CSF and EPO corrected both anemia and leukopenia and lessened subsequent zidovudine toxicity. Similarly, granulocyte macrophage-colony-stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In controlled and uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, and antineoplastic therapy. New combinations of hematopoietic stimulants are being used to decrease the toxicity from combination antiretroviral therapy with alpha interferon and cytotoxic chemotherapy in the treatment of AIDS-related malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hematopoietic growth factors as adjuncts to antiretroviral therapy. 138 Feb 56

The Epstein-Barr virus (EBV) causes infectious mononucleosis and is linked to several disparate malignancies. Prior studies on patients with multiple sclerosis (MS) showed that 100% are EBV-seropositive and that their blood contains higher antibody titers than those of controls to both transformation and lytic cycle antigens. We performed three different assays for antibodies in CSF to three major EBV antigens from patients with MS and controls. Among 93 patients with MS, 79 (85%) had CSF that reacted with a 70 kD protein, shown to be the nuclear antigen, EBNA-1, whereas only 11 (13%) of 81 EBV-seropositive controls reacted, p less than 0.001. The CSF of all 14 MS patients, unreactive on immunoblots, contained oligoclonal bands on agarose electrophoresis. Together, the two techniques exhibit 100% sensitivity in the confirmatory diagnosis of MS. We also performed amino acid searches of the Protein Identification Resource sequence database for protein homologies to EBNA. Two pentapeptide identities were found between EBNA-1 and myelin basic protein: QKRPS and PRHRD. None of more than 32,000 other proteins in the database contained both pentapeptides. In healthy EBV-seropositive persons, the EBV-specific, MHC-restricted T lymphocytes keep the EBV-containing B lymphocytes locked in the transformed state. However, in the host genetically susceptible to MS, the same population of lymphocytes might recognize and interact with either of the two identified pentapeptides, inadvertently damaging MBP.
 ...
PMID:Antibodies against Epstein-Barr nuclear antigen (EBNA) in multiple sclerosis CSF, and two pentapeptide sequence identities between EBNA and myelin basic protein. 138 Oct 67

Diethyldithiocarbamate (DDTC) is a biochemical modulating agent that protects murine bone marrow progenitor cells from the cytotoxicity of a variety of cancer chemotherapeutic agents. However, the mechanism of this protection is not well understood. Long-term human bone marrow cultures (LTBMC) were established and at day 17 treated with 30 mumol/L DDTC for 1 hour, after which DDTC was removed and replaced with complete medium. Conditioned medium was then collected 6, 12, 24, and 48 hours later and analyzed for the presence of cytokines. A time-dependent increase in granulocyte-macrophage colony-stimulating factor (GM-CSF) (12-fold), granulocyte-CSF (G-CSF) (66-fold), interleukin (IL)-6, (three-fold), IL-1 beta (161-fold), and tumor necrosis factor (TNF)-alpha (25-fold) was observed. The maximum increase for the factors other than TNF-alpha was at 24 to 48 hours posttreatment. However, TNF-alpha peaked as early as 6 hours post-DDTC. When conditioned medium from these cultures was tested in a granulocyte-macrophage progenitor cell (GM-CFC) assay, an increase in colony formation was observed that correlated with the increased levels of cytokines in the medium. The specificity of this effect was confirmed by the fact that the closely related congener bis(hydroxyethyl)dithiocarbamate was devoid of colony-stimulating activity. The addition of antibodies for TNF-alpha and/or IL-1 alpha following DDTC treatment did not inhibit the release of GM-CSF, G-CSF, or IL-6 from the LTBMC. These results suggest that DDTC accelerates bone marrow recovery following myelotoxic drug treatment via increased production of cytokines that are known to be essential for hematopoiesis.
 ...
PMID:Diethyldithiocarbamate induction of cytokine release in human long-term bone marrow cultures. 138 Dec 36

A phase II study examining the effects of human recombinant granulocyte-colony-stimulating factor (G-CSF) on the growth of colony-forming unit-granulocyte macrophage (CFU-GM) in the bone marrow and in the peripheral blood was performed in lung cancer patients treated with cisplatin-containing regimens. Treatment with G-CSF following chemotherapy significantly increased the absolute granulocyte count. No significant effect of G-CSF on either the platelet or the red blood cell count was observed. Treatment with G-CSF did not affect the CFU-GM levels in the bone marrow, but did have a significant effect on peripheral blood CFU-GM levels 14 days after initiation of chemotherapy (P less than 0.05). Four patients demonstrated a rebound increase in the level of peripheral blood CFU-GM during the first course of chemotherapy without G-CSF. In contrast, eight patients displayed increase in peripheral blood CFU-GM levels during the second course of chemotherapy with G-CSF treatment. These findings demonstrate that G-CSF is a potent stimulator of granulocyte proliferation as well as a potent agent for promoting transport of hematopoietic progenitors from the bone marrow into the peripheral blood.
Jpn J Cancer Res 1992 Jul
PMID:Granulocyte-colony-stimulating factor enhances the circulating hematopoietic progenitors in lung cancer patients treated with cisplatin-containing regimens. 138 42

Fifty-six children with various malignancies were treated subcutaneously with recombinant human granulocyte colony-stimulating factor (rhG-CSF, KRN 8601) for neutropenia induced by cancer chemotherapy. Patients received the first chemotherapy without rhG-CSF (control course). In the second course, rhG-CSF was given once daily, starting 3 days after completion of identical chemotherapy (day 3) and continuing until day 12. At day 12, the white blood counts and neutrophil counts were found to be 6.8 and 30 times higher in the rhG-CSF course than in the control course (P = .0001) Nadirs of white blood counts and neutrophils were significantly elevated in the rhG-CSF course (P = .003 and .0001, respectively). rhG-CSF administration shortened the neutropenic period in the majority of patients. Children tolerated the rhG-CSF administration well and we have hereby confirmed that rhG-CSF administration is useful for proceeding with chemotherapy in children with cancer.
 ...
PMID:Treatment of chemotherapy-induced neutropenia in children with subcutaneously administered recombinant human granulocyte colony-stimulating factor. 138 41

We have reported that polymorphonuclear leukocytes (PMN) and active oxygen species from PMN may play an important role in the mechanism of the antitumor effect of hyperthermia. At this time, we focused our experimental studies on rat AH109A carcinoma treated with hyperthermia combined with arterial injection of rhG-CSF. Rats with transplantable AH109A carcinoma at the hind leg received hyperthermia. These tumors showed mild suppression of further development only by hyperthermia. However, when arterial injection of rhG-CSF was applied together with hyperthermia, marked suppression of tumor development was observed. Our data suggest that hyperthermia combined with rhG-CSF is closely related to the generation of free radical-mediated tumor cell killing, and it can be an effective treatment for cancer.
 ...
PMID:[Role of polymorphonuclear leukocytes (PMN) and active oxygen species in hyperthermia--antitumor effect of hyperthermia combined with rhG-CSF]. 138 99

Transforming growth factor-beta 1 (TGF-beta 1) induces cell death in myeloid leukemia by apoptosis. In the M1 myeloid leukemia, this induction of apoptosis was inhibited by granulocyte colony-stimulating factor (G-CSF) or interleukin-6 (IL-6) and to a lesser extent by IL-1 alpha. IL-3 and stem cell factor/mast cell growth factor (SCF) showed only a marginal effect, and granulocyte-macrophage and macrophage CSFs (GM-CSF and M-CSF, respectively) were inactive. The induction of apoptosis by TGF-beta 1 in a different myeloid leukemia (7-M12) was inhibited by GM-CSF and IL-3 but not by the other cytokines. In the absence of TGF-beta 1, both M1 and 7-M12 leukemic cells were independent of hematopoietic cytokines for cell viability and growth. The cytotoxic compounds vincristine, vinblastine, adriamycin, cytosine arabinoside, cycloheximide, and sodium azide, some of which are used in cancer chemotherapy, induced cell death by apoptosis in both leukemias. As with TGF-beta 1, apoptosis induced by these cytotoxic compounds was inhibited by GM-CSF (7-M12 leukemia) and by G-CSF or IL-6 (M1 leukemia). Cyclosporine A decreased cell multiplication in M1 cells without inducing apoptosis, and G-CSF and IL-6 inhibited the cytostatic effect of cyclosporine A. It is suggested that the clinical use of cytokines to correct therapy-associated myelosuppression should be carefully timed to avoid protection of malignant cells from the cytotoxic action of the therapeutic compounds.
 ...
PMID:Hematopoietic cytokines inhibit apoptosis induced by transforming growth factor beta 1 and cancer chemotherapy compounds in myeloid leukemic cells. 138 3

Mutations in the Steel locus, encoding a growth factor (Steel factor or SF) or c-kit, the gene encoding its receptor, result in severe anemia in the mouse. In the present study, we have addressed the mechanism of synergistic growth activation, at the cellular level, by SF and GM-CSF using the blast cells of acute myeloblastic leukemia (AML blasts). Our data indicate that SF drastically alleviates the requirement in cell interaction for blast colony formation in most of the samples tested. Analysis of cultures performed in the presence of SF and GM-CSF at different cell concentrations, ranging from 1,000 to 20,000 cells, suggested a single limiting element, i.e., the blast clonogenic cell, while 2 or more limiting elements were found in cultures stimulated with GM-CSF alone, suggesting interacting cell populations. The presence of membrane-bound SF was detected by immunofluorescence, suggesting the possibility that secreted or membrane-bound SF may, at least in part, contribute to the density-dependent growth of AML blasts. In all samples tested, SF appears to increase the responsiveness of AML blasts to GM-CSF, as demonstrated by a 3-fold decrease of GM-CSF half efficient concentration on addition of SF to the cultures. Exposure of AML blasts to SF did not affect GM-CSF receptor expression, suggesting that this increase in GM-CSF responsiveness is likely to occur at the postreceptor level. Interestingly, 2 of 15 AML samples surveyed did not respond to SF, and were both of the myelomonocytic or monocytic subtype, classified as M4 and M5, respectively.
Cancer Res 1992 Oct 01
PMID:Product of the Steel locus can replace leukemic cell interaction. 138 39

The standard approach for epithelial ovarian cancer has been maximum cytoreductive surgery followed by combination therapy. Several prospective control studies individually failed to demonstrate improved survival advantage for the Adriamycin containing combination compare with cisplatin plus cyclophosphamide. The two drug combination of carboplatin plus cyclophosphamide will be thought to become the treatment of choice, because it is equally effective as and less toxic than a regimen of cisplatin plus cyclophosphamide. Clinical trials are also in progress with more dose-intense regimens based on considerable retrospective evidence that survival is correlated with the dose intensity of platinum compounds. Currently, high dose carboplatin plus Gm-CSF, two-drug combination of carboplatin and cisplatin and super high dose carboplatin combined with autologous bone marrow transplantation are undergoing clinical trials. Taxol and taxotere, most important cancer drugs after emergence of cisplatin compound, has been shown to have clinical activity in drug resistant ovarian cancer patients. Majority of patients even with advanced germ cell tumors of the ovary is now cured because of the development of effective platinum-based combination chemotherapy of PVB or BEP.
 ...
PMID:[Recent advances in ovarian cancer chemotherapy]. 138 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>