Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.7 (DNA polymerase)
17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of methylprednisolone (MP) on the cell kinetic response to cyclophosphamide (CP) and Adriamycin (ADR) in C3H/HeJ spontaneous mammary tumors and hematopoietic tissue was investigated. The [3H]deoxythymidine labelingg index, the primer-dependent DNA polymerase labeling index (an estimate of tumor growth fraction), and the mitotic index were determined at various intervals after treatment. Treatment consisted of CP (200 mg/kg) on Day 0 plus ADR (2 mg/kg) on Day 1 with or without MP every 12 hr for 9 doses beginning on Day 2. In tumors treated with CP and ADR alone, changes in the kinetic parameters suggested proliferative recovery between Days 3 and 4 which coincided with bone marrow recovery. In tumors treated with CP, ADR, and MP, although the timing of the hematopoietic recovery was not affected by MP, the overshoot of the [3H]deoxythymidine labelin index on Days 3 and 4 was abolished. Proliferative recovery in the tumor was delayed until after cessation of MP treatments. Cell kinetic changes in the tumor after CP, ADR, and MP were used to design effective sequential chemotherapy which obviated the hematopoietic toxicity associated with sequential therapy designed from cell kinetic changes after CP and ADR alone.
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PMID:Effect of methylprednisolone on the cell kinetic response of C3H/HeJ mammary tumors to cyclophosphamide and adriamycin. 47 17

Findings from this study using a transplantable C3H mammary tumor failed to indicate interaction relative to growth parameters between two foci present in the same host. Whether they were growing alone or in the presence of a second focus, tumor growth rates were similar until the combined mass of multiple tumors approached that which was incompatible with survival. Only then was a difference in growth observed. Cytokinetic parameters, i.e., labeling index, primer-dependent DNA polymerase index or growth fraction, DNA synthesis time, tumor doubling time, and cell cycle time, were also similar whether tumors grew alone or in the presence of a second focus. Following removal of a tumor, changes were observed within 24 hr in the kinetics of the residual focus. There was an increase in labeling index (duration approximately equal to 10 days) and primer-dependent DNA polymerase index with a decrease in the tumor doubling time. Minimal change was noted in DNA synthesis time and cell cycle time. The kinetic changes observed were reflected in a measureable increase in tumor size approximately equal to a week following tumor removal. Absence of an alteration in DNA synthesis time and cell cycle time indicates that the increase in tumor growth was probably due to a conversion of noncycling cells in G0 phase into proliferation. Relationship of the findings to the use of adjuvant chemotherapy is considered.
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PMID:Effect of surgical removal on the growth and kinetics of residual tumor. 47 22

DNA polymerase activity was studied as a function of stage of tumor growth and correlated with DNA synthesis measured by 3H-TdR uptake. Considerable variations in DNA synthesis activity occur at different growth stages and following host death. DNA alpha-polymerase activity did vary with growth stage in the ascites tumor. However, it did not have a clear correlation with DNA synthesis or with tumor growth. No striking fall in DNA polymerase enzyme levels occurred as the ascites tumor reached stationary phase in contrast to reports in some cell culture systems. A decrease occurred with advanced tumor stage and after host death. DNA beta-polymerase activity did not change with tumor growth stage.
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PMID:DNA polymerases during tumor growth. 61 18

Evidence is presented that a number of sesquiterpene lactones isolated from plants and synthesized pyrimidines containing the alpha-methylene-gamma-lactone moiety are potent inhibitors of Walker 256 carcinosarcoma and Ehrlich ascites tumor growth and marginal inhibitors of P-388 lymphocytic leukemia and Lewis lung tumor growth. In vitro aerobic basal respiration and oxidative phosphorylation processes of Ehrlich ascites cells were inhibited by these agents as well as deoxyribonucleic acid polymerase and thymidylate synthetase enzymatic activities. These studies indicate that the alpha-methylene-gamma-lactone moiety, the beta-unsubstituted cyclopentenone ring, and the alpha-epoxycyclopentanone system are the essential moieties for inhibition of these biochemical parameters.
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PMID:Antitumor agents XXX: Evaluation of alpha-methylene-gamma-lactone-containing agents for inhibition of tumor growth, respiration, and nucleic acid synthesis. 69 Aug 26

Transplantable fibrosarcomas were developed in two B-locus-defined chicken strains from primary tumors induced by im injection of 2 mg 7,12-dimethylbenz[a]anthracene in 0.1 ml dimethyl sulfoxide into 1- to 2-week-old chicks. Viruses were not important factors in transmission of these tumors as evidenced by 1) transplantability only within the chicken strain of origin, 2) lack of evidence for a filterable agent, 3) maintenance of donor karyotypic characteristics upon transplantation, 4) lack of DNA polymerase and avian leukosis virus group-specific protein production in vitro. Bursectomized inbred SC chickens had a higher incidence of tumor induction than did normals of the same strain. Although the exact interpretation of this finding posed some problems, as discussed, an important function of enhancing antibody in tumor growth appeared excluded.
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PMID:Chemical carcinogen-induced transplantable fibrosarcomas in histocompatible chickens. I. Incidence of tumor induction in normal and bursectomized chickens. 82 48

Cell kinetics in spontaneous C3H/HeJ mammary tumors of retired-breeder mice was studied by in vivo and in vitro techniques. The [3H]TdR labeling index (LI), the DNA synthesis time (TS), and the primer-dependent DNA polymerase assay LI [an in vitro estimate of tumor growth fraction (GF)] were compared to similar measurements made in vivo. These measurements as well as the calculated cell kinetic parameters derived from these data were not different in in vivo and in vitro studies. Furthermore, the cell kinetic parameters in tumors classified histologically as type A or type B mammary tumors were also similar. Although considerable variation in volume doubling times (Td's), [3H]TdR LI's, potential doubling times, cell cycle times (Tc's), and cell loss was found, Ts's were similar in all mammary tumors. No correlation between tumor volume or tumor weight and cell kinetic parameters was seen. However, the most slowly growing tumors (i.e., tumors with the longest Td's) tended to have the lowest [3H]TdR LI's, the longest Tc's, and the highest cell loss factors. No correlation was found between the GF and Td. However, tumors with the most rapidly proliferating cell populations tended to have the highest GF's.
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PMID:Cell kinetics in vivo and in vitro for C3H/He spontaneous mammary tumors. 90 95

The tumor growth fraction measured by the percentage labeled mitoses method has been determined in transplantable solid and ascites murine tumors, the latter being measured at different times after transplantation. These values were compared to an in vitro, autoradiographic assay that determines the fraction of cells in a given population (primer-available DNA-dependent DNA polymerase index) that have both nuclear DNA-dependent DNA polymerase and DNA capable of acting as primer-template. It appears that almost all cells with a short G1 phase duration (less than 19 hr) that are within the proliferative cycle are primer-available DNA-dependent DNA polymerase positive. The results of the comparison indicate that the primer-available DNA-dependent DNA polymerase index estimation of growth fraction is very nearly identical to the growth fraction measured by the percentage labeled mitoses method.
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PMID:Estimation of tumor growth fraction in murine tumors by the primer-available DNA-dependent DNA polymerase assay. 127 47

Immunohistochemical detection of cell cycle-related markers for estimation of tumor growth fractions using paraffin-embedded tissue sections would have applications in experimental and clinical pathology as an in situ histologic alternative to flow cytometry. The monoclonal antibodies 19A2 and PC10 detect the proliferating cell nuclear antigen (PCNA/Cyclin), an auxiliary protein to DNA polymerase-delta. In a prospective group of uniformly handled, formalin-fixed malignant lymphomas we previously demonstrated 19A2 to be a reliable marker of proliferative activity similar to Ki-67 in frozen tissue. The present study examines the applicability of this technique in archival formalin-fixed material. Studies on tonsilar tissue revealed that formalin fixation beyond 30 hours adversely affected reactivity of 19A2, possibly explaining the variable results in nonuniformly fixed archival material. We found that only 27 (56%) of 48 archival cases of infiltrating ductal carcinoma showed sufficient reactivity with 19A2 to permit reliable quantification of the tumor growth fraction. Acid pretreatment with 2N HCl had no apparent effect on 19A2 reactivity. Using both antibodies on a group of 32 archival lymphomas, carcinomas, and sarcomas, significantly more biopsies stained reliably for PC10 (84%) than for 19A2 (72%; P < 0.036). Further, none of the cases that did not react with PC10 reacted with 19A2. PC10 may recognize a different epitope of PCNA/Cyclin which may be more resistant to alterations by fixation. In the 23 cases that reliably stained for both markers, largely carcinomas, there was excellent correlation between estimated growth fractions (r = 0.96). Although immunostaining provides a useful way to estimate tumor growth fractions in paraffin-embedded tissues, modifications of technique and cautious interpretation of results are advisable when using archival material.
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PMID:Estimation of tumor growth fractions in archival formalin-fixed, paraffin-embedded tissues using two anti-PCNA/Cyclin monoclonal antibodies. Factors affecting reactivity. 128 22

The present experiments were conducted to determine the effects of cyclophosphamide (150 mg/kg) on the pathophysiology of RIF-1 solid tumors and to determine the temporal relationship between treatment mediated changes in tumor vascular physiology, cell proliferation, and chemoresponsiveness in vivo. Capillary permeability and plasma and extracellular water volumes were determined by a 125I-bovine serum albumin, 51Cr-EDTA double isotope dilution assay at various intervals after cyclophosphamide. Tumor blood flow and exchangeable erythrocyte vascular volumes were determined by 86RbCl distribution and 51Cr-labeled erythrocyte dilution methods. Cell proliferation in RIF-1 tumors, assessed by [3H]thymidine labeling index and tumor growth fraction (primer-dependent DNA polymerase labeling assay) measurements, was inhibited for up to 3 days by cyclophosphamide. Although tumor regrowth was not apparent until Day 10, cell kinetic studies indicated proliferative recovery in the surviving cell population on Days 4 and 5 after treatment. Increases in tumor blood flow and tumor vascular volumes were temporally coincident with this proliferative response. In split-dose experiments, the time-dependent increases in the chemoresponsiveness of RIF-1 tumors, after cyclophosphamide, may be due not only to the increased proliferation of repopulating cells, but also to vascular responses attendant with cytoreduction.
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PMID:Effect of cyclophosphamide on the pathophysiology of RIF-1 solid tumors. 339 Aug 14

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


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