Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic myelogenous leukemia (CML) is a stem cell disease which, on a clinical level, progresses from the release from growth control of normally differentiated cells (a preleukemic state) to an acute leukemia. On a molecular level, the evolution of CML to acute leukemia is a multistep process. We propose that an early step, at the stem cell level, is acquisition of the ability for gene movement, which allows subsequent submicroscopic and chromosomal rearrangements that cause changes in the growth characteristics and regulation of the stem cell. A specific platelet DNA polymerase (PDP - reverse transcriptase) may play a role in gene movement. The characteristic reciprocal translocation of chromosomes #9 and #22, causing the activation of the c-abl oncogene, appears to be responsible for the uncontrolled cellular growth. Yet, other growth factors (e.g., platelet derived growth factor) and activated oncogenes (e.g., c-sis) must be responsible for the stimulation, progression, and variability seen during the course of the disease. Because CML is a progressive disease with clinically definable stages, CML appears to be a model system for the study of the molecular basis of the progression of preleukemia to leukemia specifically, and preneoplasia to aggressive neoplasia in general.
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PMID:Implications of retroviral and oncogene activity in chronic myelogenous leukemia. 243 4

The tumor proliferative activity of 74 previously untreated epithelial ovarian carcinomas was evaluated by the thymidine labeling index (TLI) and the primer-dependent alpha DNA polymerase assay (PDP-LI). The median TLI and PDP-LI were 2% (0.1 to 28.0) and 10% (3.0 to 80.0), respectively. The TLI was significantly correlated to tumor grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and residual disease. However, neither the TLI nor the PDP-LI was a predictor of survival. A higher response rate was observed in the case of rapidly proliferating tumors: an objective response (OR) was observed in 38.4% of the patients with a low TLI and in 53.6% of the patients with a high TLI. The advantage of an OR in favor of the high TLI group was significant for patients treated with regimens containing doxorubicin (high TLI, 72.2% OR; low TLI, 40% OR; P = 0.03).
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PMID:Cell kinetics in ovarian cancer. Relationship to clinicopathologic features, responsiveness to chemotherapy, and survival. 276 16

The feasibility of a cytokinetic chemotherapy based on estrogenic recruitment has been evaluated in 5 patients, affected by locally advanced breast cancer with low or absent receptor content. Tumor proliferative activity was evaluated by the thymidine labeling index (TLI) and the primer-dependent alpha DNA polymerase assay (PDP-LI) which gives an in vitro estimation of tumor growth fraction. The patients have been treated with diethylstilbestrol (DES) 1 mg/die. for 3 days, followed by FAC (5-Fluorouracil 600 mg/m2, Adriamycin 50 mg/m2, Cytoxan 600 mg/m2) i.v. on day 4 q. 21 days. Radical surgery was performed after 3 DES-FAC regimens. Tumor biopsies for evaluation of tumor proliferative activity were performed immediately before and after DES and 24 h after chemotherapy. Our results demonstrate that DES was able to induce an increase in TLI in 3/5 of the patients while the PDP-LI was significantly increased in 5/5 of the patients; subsequent chemotherapy induced a sharp decrease in tumor proliferation. These results provide the rationale for the design of cytokinetic regimens where chemotherapy is administered at the time of estrogen induced tumor cell recruitment.
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PMID:Estrogen induced expansion of the growth fraction in receptor negative human breast cancer. 409 31