Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The respective pretreatment prognostic impacts of the following markers were evaluated in 125 patients with small cell lung cancer (SCLC): lactic dehydrogenase (LDH), serum thymidine kinase (S-TK), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and tissue polypeptide antigen (TPA). More traditional clinical and serologic markers were also evaluated. Univariate analysis showed that all of the biochemical markers mentioned above, the Karnofsky index (KI) and the patient's sex were related to both the stage of disease (limited/extensive disease: LD/ED) and to survival. The strongest marker for the clinical stage was S-TK, whereas TPA showed the strongest relationship with survival. Multivariate analyses produced a model consisting of S-TK, CEA, NSE, and the patient's sex for determining the clinical stage. To compare the prognostic capacity of easily determined biochemical and simple clinical variables to the more resource-demanding variable of the clinical stage, three multivariate analyses in relation to survival were performed: (1) biochemical markers and simple clinical variables; (2) LD/ED and simple clinical variables; and (3) all available variables. The model obtained from the first analysis included TPA, KI, age, and the patient's sex; the model from the second analyses included LD/ED, patient's age, and KI; and the model from the third analysis, TPA, KI, age, sex, and LD/ED. Indices based on these three multivariate models were calculated for each patient and the prognostic capacity of these indices was compared. Pretreatment serum marker levels also had the capacity to predict both the grade and the duration of the response to therapy.
 ...
PMID:Clinical and serologic markers of stage and prognosis in small cell lung cancer. A multivariate analysis. 216 41

The serum levels of neuron specific enolase (s-NSE) and thymidine kinase (s-TK) were studied in detail in patients with small cell lung cancer (SCLC) to evaluate as to whether their combined use may aid to diagnosis and follow-up of this particular tumor. Only s-NSE could differentiate between SCLC and non-small cell lung cancer (NSCLC) or benign pulmonary diseases (BPD) to some extent, pathologic serum concentrations occurring in 81%, 17%, and 0%, respectively. The comparable figures for s-TK were 62%, 24%, and 28%, respectively. Serum NSE decreased and increased paralleling tumor regression and progression, respectively, except when brain metastases were present. Alterations of s-TK, in contrast, did not usually mirror the course of disease. During initial chemotherapy (CT) a transitory increase of serum levels was observed for both NSE and TK. Monitoring, based on daily blood samples, showed comparable peaks only for s-TK during the following CT cycles, whereas s-NSE was within the normal range even when tumor mass was still present. Those subsequent s-TK peaks under CT may be due to tumor cell lysis as a result of CT indicating the efficacy of treatment by this way. Rapidly proliferating tissues such as bone marrow or bowel mucosa, however, have also to be considered as possible sources of s-TK.
 ...
PMID:Neuron-specific enolase and thymidine kinase as an aid to the diagnosis and treatment monitoring of small cell lung cancer. 253 35

We analyzed serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and thymidine kinase (TK) levels in 22 patients with small cell lung cancer. Tumor proliferation was expressed as the proportion of S-phase cells (SPF), determined by DNA flow cytometry, from concomitantly taken biopsy samples. A positive correlation between serum NSE (r = 0.41) or LDH (r = 0.65, p = 0.05) levels and tumor SPF was noted, but was not found between serum TK levels and the SPF. The correlation between NSE and SPF was even more pronounced if only patients with extensive disease were considered (r = 0.77). The serum NSE and LDH, but not TK levels, were significantly greater in the patients with extensive disease (NSE 50.4 ng/ml, LDH 621 U/ml) compared to the patients with limited disease (NSE 21.0 ng/ml, LDH 272 U/ml, p = 0.05). Our results suggest that the combined determination of serum LDH and NSE levels gives valuable data on the primary tumor mass and its proliferative activity in small cell lung cancer.
 ...
PMID:Correlation between serum tumor marker levels and tumor proliferation in small cell lung cancer. 284 99

Serological tumor markers may become widely used as inexpensive and non-invasive methods of cancer detection. Markers of current interest for small cell lung cancer (SCLC) comprise enzymes, peptides, proteins, and carbohydrates. None of the serological markers for SCLC have yet proven to be of diagnostic value and at present their use is limited to monitoring disease and indicating prognosis. However, whilst serological markers related to the metabolic state of SCLC cells, such as neuron-specific enolase, serum thymidine kinase and tissue polypeptide antigen, may only be used for monitoring patients and for estimating prognosis, the other serological markers under current investigation may be used to indicate new treatment forms. Several novel approaches, including interference in the autocrine growth-regulating loop of SCLC by either peptides or antibodies, have been tried, SCLC is a highly heterogeneous tumor with respect to antigen expression, regulation of growth, and differentiation state. It is therefore important that new interventions are directed against both antigen-positive and antigen-negative tumor cells. For instance, radioisotopes or enzymes coupled to antibodies may be effective by exerting toxicity at some distance from the target. Antigens expressed on SCLC cells, such as peptide receptors involved in growth regulation, carbohydrate antigens like Lewis antigens, carcinoembryonic antigen and the ganglioside fucosylGM1, provide potential targets for antibody-conjugated therapy.
 ...
PMID:Serological tumor markers for small cell lung cancer and their therapeutic implications. 794 58

Herpes simplex virus thymidine kinase (HSV-TK) gene was ligated with four repeats of the Myc-Max response elements (a core nucleotide sequence CACGTG), and its utility for gene therapy was examined by the treatment of either c-, L- or N-myc-overexpressing the small cell lung cancer (SCLC) cell line with ganciclovir (GCV). The chloramphenicol acetyltransferase assay demonstrated that the overexpression of any myc genes activated transcription from the CAT gene depending on the Myc-Max binding sites. The transduction of the HSV-TK gene ligated with the CACGTG core rendered all three SCLC lines to be more sensitive to GCV than parental ones in vitro. In addition, the growth of c- or L-myc-overexpressing SCLC cells containing the hybrid HSV-TK gene were significantly suppressed by GCV in vivo. When parental SCLC cells were mixed with HSV-TK-expressing tumor cells at a ratio of 1:3, GCV treatment inhibited tumor growth by 90% compared with parental cells only, indicating the existence of the "bystander effect." These data suggest that the CACGTG-driven HSV-TK gene may be useful for the treatment of SCLC overexpressing any type of myc family oncogenes.
 ...
PMID:Eradication of Myc-overexpressing small cell lung cancer cells transfected with herpes simplex virus thymidine kinase gene containing Myc-Max response elements. 854 91

Recent clinical trials of gene therapy for patients with thoracic cancers have shown that these treatments were well tolerated with minimal side effects and that we need to further enhance specificity as well as efficiency of gene transfer to target cancer cells. We previously reported that myc-overexpressing SCLC cell lines became selectively sensitive to ganciclovir (GCV) by transducing the herpes simplex virus thymidine kinase (HSV-TK) gene under the control of the Myc-Max response elements (a core nucleotide sequence, CACGTG) and that this construct (MycTK) could be utilized to develop a novel treatment against chemo-radio-resistant SCLC. We report here in vivo antitumor effects and safety of a replication-deficient adenoviral vector containing the Myc-Max binding motif (AdMycTK) on SCLC cells. In vitro infection with AdMycTK selectively rendered myc-overexpressing SCLC cell lines 63- to 307-fold more sensitive to GCV. In vivo injections with AdMycTK followed by GCV administration markedly suppressed the growth of myc-overexpressing tumors established in the subcutis or in the peritoneal cavity of athymic mice. On the other hand, infection with AdMycTK did not significantly affect either in vitro GCV sensitivity of the cells expressing very low levels of the myc genes or the growth of their subcutaneous tumors. Moreover, we observed no apparent side effects of this treatment including body weight loss or biochemical abnormalities in contrast to the treatment with AdCATK that conferred strong but nonspecific expression of the HSV-TK gene. These results suggested that AdMycTK/GCV therapy is effective on SCLC patients whose tumors overexpress myc family oncogenes.
 ...
PMID:Adenovirus-mediated gene therapy specific for small cell lung cancer cells using a Myc-Max binding motif. 1127 91

Cisplatin (CDDP) resistance is one of the major impediments in cancer chemotherapy. In an attempt to define this complex mechanism(s) of resistance, we have identified 7 cDNA fragments which are overexpressed in CDDP resistant small cell lung cancer cell line (SR-2) using PCR selected cDNA subtraction. One of these fragments was identical with nucleotide 3657-4042 of MRP4. The other fragments share sequence homology with elongation factor alpha, human placenta villi cDNA, heat shock protein (Hsp70), ribosomal RNA, BNP1 brain specific Na-dependent inorganic phosphate cotransporter and telomeric catalytic subunit. Examination of other MRP members (MRP1, 2, 3, 5, 6) did not show discernable differences in their expression between the parental (SCLC1) and the CDDP-resistant variant (SR-2). Full length MRP4 cDNA was obtained from SCLC1 and SR-2. Both cell lines carry a point mutation at nucleotide 3532 while SR-2 carries two additional mutations at 3228 and 3246. Since MRP4 is known to transport azidiothymidine (AZT) and overexpression of MRP4 confers AZT resistance, we have studied growth inhibitory effects of AZT and [3H]-AZT accumulation. Interestingly, SR-2 is more sensitive to AZT while accumulating lesser amounts of [3H]-AZT. The thymidine kinase activity is similar in both cell lines. Thus, the increased sensitivity to AZT in SR-2 could not be solely due to mutation of MRP4. These findings are most likely due to the inhibitory effects of telomere catalytic subunit by AZT. Thus, certain biochemical changes induced by CDDP can be explored for future treatment to overcome this form of resistance.
 ...
PMID:Overexpression of mutated MRP4 in cisplatin resistant small cell lung cancer cell line: collateral sensitivity to azidothymidine. 1279 91

Thymidine kinase is the key enzyme in salvage pathway for pyrimidine nucleotide synthesis. High activities of thymidine kinase have been found in rapidly proliferating normal, neoplastic tissues and sera from patients with various diseases including lymphoma, leukemias and small cell lung cancer. We investigated the serum thymidine kinase activities and the colorectal carcinomas in rats treated with 1,2-dimethylhydrazine. The positive correlations between serum thymidine kinase activities and numbers of total and large tumors were observed. These findings suggest the measurement of serum thymidine kinase activity may be clinically valuable in an early stage of the colonic carcinogenesis.
 ...
PMID:Serum thymidine kinase as a tumor marker of colorectal carcinogenesis induced with 1,2-dimethylhydrazine in rats. 2159 7

E2F-1, a key transcription factor necessary for cell growth, DNA repair, and differentiation, is an attractive target for development of anticancer drugs in tumors that are E2F "oncogene addicted". We identified a peptide isolated from phage clones that bound tightly to the E2F-1 promoter consensus sequence. The peptide was coupled to penetratin to enhance cellular uptake. Modeling of the penetratin-peptide (PEP) binding to the DNA E2F-1 promoter demonstrated favorable interactions that also involved the participation of most of the penetratin sequence. The penetratin-peptide (PEP) demonstrated potent in vitro cytotoxic effects against a range of cancer cell lines, particularly against Burkitt lymphoma cells and small cell lung cancer (SCLC) cells. Further studies in the H-69 SCLC cell line showed that the PEP inhibited transcription of E2F-1 and also several important E2F-regulated enzymes involved in DNA synthesis, namely, thymidylate synthase, thymidine kinase, and ribonucleotide reductase. As the PEP was found to be relatively unstable in serum, it was encapsulated in PEGylated liposomes for in vivo studies. Treatment of mice bearing the human small cell lung carcinoma H-69 with the PEP encapsulated in PEGylated liposomes (PL-PEP) caused tumor regression without significant toxicity. The liposome encapsulated PEP has promise as an antitumor agent, alone or in combination with inhibitors of DNA synthesis.
 ...
PMID:Antitumor and modeling studies of a penetratin-peptide that targets E2F-1 in small cell lung cancer. 2379 70