Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lonidamine (LND), previously reported as a useful antitumor substance in combination with physical or chemical agents, has been studied for its capacity in increasing pharmacological elimination in vitro of residual tumor cells from human bone marrow. Different drugs were tested in association with LND against mixtures of human bone marrow and a tumor cell line, clonogenic human leukemic blast progenitors, and normal human bone marrow precursors. The results demonstrated that LND increased the efficacy of anthracycline derivatives (Adriamycin, Mitoxantrone) both on the tumor cell line and on the leukemic blast progenitors, while VP-16 or ASTA-Z 7654 was not affected by the same substance. The toxicity on normal stem cells reflected that of each drug and was not modified by the addition of LND. While a consistent dose-dependent CFU-GM reduction was observed immediately after treatment with the different drugs, a complete recovery was reached after 7 and 14 days of long-term marrow cultures. Because of the low toxicity and the efficacy demonstrated in association with certain agents in increasing tumor cell elimination in vitro, LND could play an important role in in vitro purging prior to autologous bone marrow transplantation.
Exp Mol Pathol 1989 Apr
PMID:In vitro pharmacological purging of human bone marrow is enhanced by the use of lonidamine. 270 84

Some patients in apparent complete remission of hairy cell leukemia (HCL) after 2-chlorodeoxyadenosine (2-CdA) treatment may have minimal residual disease (MRD). This study examines detection of minimal residual disease by immunohistological staining using the monoclonal antibody (MoAb) B-ly 7 in 11 patients with complete remission of hairy cell leukemia (HCL) after 2-CdA therapy administered between 1990 and 1993. In all 11 cases, residual hairy cells could be detected by MoAb B-ly 7 (0.1 to 7.5%, median 0.65%). At a follow-up period of 7 - 29 months (median 19.3), 9 of these patients remained in complete remission, whereas 2 patients relapsed 22 and 27 months after 2-CdA therapy. To determine whether flow-cytometric analysis of hairy-cells in bone marrow aspirates and peripheral blood cells are comparable with results obtained by immunostaining with B-ly 7 in bone marrow biopsies, available data using CD-19/CD-11c double-staining were analyzed. In 5 of 10 cases no hairy-cells could be detected in bone marrow aspirates, and in 6 partly different cases no hairy-cells were detectable in peripheral blood using flow-cytometry, although immunostaining of bone marrow biopsies using B-ly 7 revealed hairy-cells (ranging form 0.1 to 7.5%) in these cases. These results indicate that therapy with 2-CdA does not eradicate hairy cell leukemia despite complete remission according to conventional criteria. Minimal residual disease might be responsible for subsequent relapse. We conclude that routine immunohistological examination of bone marrow biopsies with B-ly 7 should be performed for assessment of MRD. Flow cytometric investigations of mononuclear cells of bone marrow aspirate or peripheral blood seem valuable for regular long term monitoring of MRD, but does not substitute for immunostaining of bone marrow biopsies.
Blood Cells Mol Dis 1995
PMID:Minimal residual disease in hairy-cell leukemia after treatment with 2-chlorodeoxyadenosine. 884 43

The polymerase chain reaction (PCR) has been applied to detect occult leukemia (ALL) cells in patients with acute lymphoblastic leukemia who are otherwise considered in complete remission by traditional morphological examination of bone marrow specimens. The combined data from the clinical studies published to date suggest that a consistent pattern for residual disease disappearance over many months exists for patients who remain in complete remission for an extended period of time. Conversely, a pattern of residual disease persistence and reappearance preceding clinical findings exists for the majority of patients who ultimately relapse. The ability to detect residual ALL disease near the end of chemotherapy or after the completion of treatment in some patients who otherwise are deemed likely to be cured of their malignancy raises the possibility that mechanisms other than leukemia cell cytotoxicity are influencing the outcome for this disease.
Cytokines Mol Ther 1995 Mar
PMID:Monitoring residual disease in acute lymphoblastic leukemia: therapeutic implications. 938 65

Over the last three decades, acute lymphoblastic leukemia (ALL) of childhood has turned from a once fatal condition into a disease that can be cured in about two-thirds of patients. Nevertheless, about 30% of these children relapse with a dismal prognosis. Achievement of complete remission is an essential step in successful therapy. However, patients in complete remission as defined by morphologic criteria can still harbor more than 10(9) leukemic cells. We have recently shown that residual disease is detected in most patients after completion of therapy. The amount of persistent 'indolent' disease that is actually present in a particular patient and the degree to which it must be reduced to maintain a long-term remission is largely unknown. In order to address this question, and hence to tailor efficient therapy in accordance with the needs of the individual patient, a multitude of techniques for the detection of residual disease have been developed over the last few years. The most commonly used techniques are the polymerase chain reaction (PCR) assays. These sensitive assays have revolutionized this area of research. The heterogeneity of the results obtained, however, still precludes widespread clinical applicability of these techniques.
Cytokines Cell Mol Ther 1998 Jun
PMID:Residual disease in acute lymphoblastic leukemia of childhood: methods of detection and clinical relevance. 968 Dec 46

One of the major obstacles to the successful outcome of autologous bone marrow transplantation (ABMT) is the high relapse rate, which is most likely due to the lack of a graft-versus-tumor effect. The amplification of cell-mediated effector mechanisms against residual tumor cells is one of the ways to reduce relapse rates post ABMT at the stage of minimal residual disease. Granulocyte-monocyte colony-stimulating factor (GM-CSF) is a key cytokine that plays a major role in cytotoxicity and in the activation pathways of monocytes, macrophages, dendritic cells and tumor-infiltrating lymphocytes. Therefore it may be used for manipulating the immune system to fight against cancer. The activities of GM-CSF on monocytes-macrophages, dendritic cells and recruited components of the immune system are described in the context of the development of improved strategies for conferring enhanced resistance to a tumor-bearing host following autologous or allogeneic bone marrow transplants.
Cytokines Cell Mol Ther 1998 Sep
PMID:The implications of granulocyte-monocyte colony-stimulating factor (GM-CSF) in cytotoxicity of bone marrow transplantation. 982 45

The t(14;18) translocation and its molecular counterpart, the bcl-2/IgH gene rearrangement, are highly characteristic of follicular non-Hodgkin lymphomas. The identification of the tumor-specific t(14;18) clone is mandatory for any molecular studies on residual disease because of the existence of circulating t(14;18)-bearing benign cells. In this study, the ability to specifically polymerase chain reaction (PCR) amplify t(14;18) with DNA purified from tissues fixed with Holland Bouin fluid is demonstrated. The specificity of the PCR product was confirmed by internal probe hybridization and with comparison of the nucleotidic sequences of this PCR product with those obtained from the corresponding frozen material. Although the sensitivity of the technique is 50% to 60%, paraffin-embedded tissues fixed with bouin fluid may be a good alternative to frozen tissues to detect t(14;18) in tumors.
Diagn Mol Pathol 1998 Jun
PMID:Polymerase chain reaction diagnosis of t(14;18) from paraffin-embedded tissues fixed with Holland Bouin fluid. 983 76

Chronic myelogenous leukemia (CML) is characterized by a balanced translocation that leads to the formation of the the BCR-ABL fusion gene. Although autografts can prolong the life of CML patients, patients relapse owing to malignant cells that persist in the graft and the host. This review discusses various experimental strategies that target the BCR-ABL gene or gene products that are downstream of it. Various strategies have been adopted to block BCR-ABL at the gene, mRNA and protein level. One promising strategy involves the cotransduction of a patient's hematopoietic stem cells (HSCs) with anti-BCR-ABL antisense sequences and a drug resistance gene. This might allow for the elimination of any residual disease in the graft or host by chemotherapy while rendering any drug-resistant, malignant CML HSCs functionally normal.
Mol Med Today 1999 Aug
PMID:Gene therapy for chronic myelogenous leukemia. 1043 Nov 69

Between December 1996 and September 1998, 13 patients with advanced recurrent malignant brain tumors (9 with glioblastoma multiforme, 1 with gliosarcoma, and 3 with anaplastic astrocytoma) were treated with a single intratumoral injection of 2 x 10(9), 2 x 10(10), 2 x 10(11), or 2 x 10(12) vector particles (VP) of a replication-defective adenoviral vector bearing the herpes simplex virus thymidine kinase gene driven by the Rous sarcoma virus promoter (Adv.RSVtk), followed by ganciclovir (GCV) treatment. The VP to infectious unit ratio was 20:1. Our primary objective was to determine the safety of this treatment. Injection of Adv.RSVtk in doses <==2 x 10(11) VP, followed by GCV, was safely tolerated. Patients treated with the highest dose, 2 x 10(12) VP, exhibited central nervous system toxicity with confusion, hyponatremia, and seizures. One patient is living and stable 29.2 months after treatment. Two patients survived >25 months before succumbing to tumor progression. Ten patients died within 10 months of treatment, 9 from tumor progression and 1 with sepsis and endocarditis. Neuropathologic examination of postmortem tissue demonstrated cavitation at the injection site, intratumoral foci of coagulative necrosis, and variable infiltration of the residual tumor with macrophages and lymphocytes.
Mol Ther 2000 Feb
PMID:Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors. 1093 31

A model of mouse acute myeloid leukemia (mAML) was used to study the effector mechanism mediating the graft-versus-leukemia (GVL) effects in recipients of allogeneic bone marrow cells (BMC). mAML-bearing SJL/J (H-2s) mice were lethally irradiated and then transplanted with a mixture of BMC and spleen cells (SC) derived from normal syngeneic or allogeneic mice. To augment the GVL effect, recipients were injected intraperitoneally with recombinant human interleukin-2 (rIL-2) (1.2 x 10(5) IU) for 3 consecutive days, starting one day post BMC + SC transplantation. Spleen cells from treated recipients were adoptively transferred to untreated secondary SJL/J mice to test for the existence of residual tumor cells. All the secondary recipients of SC from mAML-bearing SJL/J mice rescued with syngeneic (SJL/J) or allogeneic (B10.S) BMC+SC (H-2s) differing at minor antigens of the histocompatibility complex (MiHC) developed leukemia and died. In sharp contrast, none of the secondary recipients of SC obtained from identical mAML-bearing mice rescued with B10.S BMC + SC but activated in vivo with IL-2 developed leukemia. Adoptive recipients of SC obtained from mAML-bearing recipients of major histocompatibility complex (MHC)-disparate (C57BL/6, H-2b) cells remained free of leukemia regardless of the use of rIL-2. In parallel with the in vivo findings, a 4-day in vitro exposure of splenocytes to 6 x 10(3) IU/ml rIL-2 resulted in a 5- to 20-fold increase in the frequency of alloreactive cytotoxic T-lymphocyte (CTL) precursors (CTLp) across MiHC and MHC barriers and a 2- to 6-fold increase in their cytotoxic activity. Our data suggest that augmentation of GVL effects by rIL-2 may be due to CTL activation by rIL-2, not excluding the potential beneficial role of rIL-2-activated allogeneic natural killer cells and MHC non-restricted killer cells. Cumulatively, our results suggest potentially beneficial effects of rIL-2, when used jointly with bone marrow transplantation or allogeneic cell therapy, on eradication of leukemia.
Cytokines Cell Mol Ther 2000 Sep
PMID:Correlation between enhancement of graft-versus-leukemia effects following allogeneic bone marrow transplantation by rIL-2 and increased frequency of cytotoxic T-lymphocyte precursors in murine myeloid leukemia. 1114 Aug 83

Adenoviral-mediated gene therapy delivery, combining the herpes simplex virus thymidine kinase gene (Ad-tk) with gancyclovir, has been evaluated as a treatment modality for numerous tumors in the laboratory and in the clinics. As a single modality, gene therapy has shown some promising local and systemic results but no curative success. Surgery is the standard of care for many solid tumors. However, minor residual tumor following surgical resection can lead to local recurrence, and surgery is neither efficient nor plausible for metastatic disease. In this study, two tumor models were used to evaluate the effects of Ad-tk gene therapy as an adjuvant to surgery. Subcutaneous mammary- and prostate-derived tumors were produced in syngeneic mice. To evaluate systemic effects, tumor cells were injected intravenously, with subsequent formation of lung nodules. The subcutaneous tumors were surgically resected and the tumor bed was bathed with saline or Ad-tk. The animals were evaluated for toxicity, local tumor recurrence, survival, and lung nodule formation. No evidence of additional toxicity was observed. In the less aggressive mammary model, the time to recurrence was increased from 11.7 (+/-1.0) days to 22.7 (+/-5.5) days. In the prostate model, recurrence went from a mean of 17.3 (+/-5.6) to 22.6 (+/-6.8) days. Survival was also improved from a mean of 19.7 (+/-1.1) to 32.3 (+/-4.8) and 26.1 (+/-5.0) to 34.1 (+/-6.1) days in the mammary and prostate models, respectively. Evidence of systemic benefits from the use of adjuvant Ad-tk therapy was demonstrated by a significant reduction in lung nodules from a mean of 17 to 3.5. These results suggest that Ad-tk gene therapy may be a useful adjuvant for patients undergoing surgery for treatment of cancer.
Mol Ther 2001 Apr
PMID:In vivo surgical resection plus adjuvant gene therapy in the treatment of mammary and prostate cancer. 1131 10


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