UMLS:C0242379 - FACTA Search

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

Query: UMLS:C0242379 (lung cancer)
71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two adenocarcinoma cell lines were established from metastatic lymph node of lung cancer patients. The cell lines were named NUTLC-1 and NUTLC-3. They were found to have the following biological characterization and sensitivity to anticancer agents by comparison with clinical effect of the drugs on each donor patient: 1) By chromosomal analysis, the tumor cells of two cell lines were human-origin cells. Number of chromosomes of these cell lines ranged from 67 to 77 in NUTLC-1 cells and from 61 to 66 in NUTLC-3 cells, with the modal numbers of 73 and 64, respectively. 2) The tumor cells of the two cell lines were heterotransplanted subcutaneously into nude mice, but, no natural distant metastasis was observed 2 months after transplantation. 3) Sensitivity to anticancer agents on NUTLC-1 and NUTLC-3 cells differed individually according to methylthiazol tetrazorium (bromide) (MTT) colorimetric assay. NUTLC-1 cells were sensitive to Mitomycin C (MMC) and Adriamycin (ADM), and insensitive to Cisplatinum (CDDP), 5-Fluorouracil (5-FU) and Etoposide (VP-16). Antitumor effect of CDDP and 5-FU on recurrent tumor of donor patient was not observed clinically. NUTLC-3 cells were sensitive to CDDP, MMC and ADM, and insensitive to 5-FU and VP-16. Sensitivity to CDDP and MMC on NUTLC-3 cells also correlated to clinical effect of the drugs on the donor patient. From these results, it appears that these new cell lines are useful materials for studies on lung cancer.
...
PMID:Characteristics of the two newly established cell lines of human pulmonary adenocarcinoma and their sensitivity to anticancer agents. 802 20

Our purpose was to determine the ability of an etoposide-cisplatin (EP )-based regimen to salvage patients with limited and extensive small-cell lung cancer who are incomplete responders to cyclophosphamide-Adriamycin-vincristine-etoposide (CAVE) chemotherapy, and to determine the ability of thoracic radiation therapy (TRT) to salvage CAVE and EP incomplete responders. Fifty-eight patients with small-cell lung cancer (33, limited disease; 25, extensive disease) were entered on this Phase II study between November 1984 and December 1987. Patients received three cycles of CAVE chemotherapy, followed by two cycles of CEPi (cyclophosphamide-etoposide-cisplatin (infusional) and two cycles of CE (cyclophosphamide-etoposide) in conjunction with TRT and prophylactic cranial irradiation (PCI). The overall response rate to CAVE was 62% [5% complete response (CR), 57% partial response (PR) + regression (REGR)]. Of the patients who failed to achieve a CR with CAVE, 81% responded to CEPi (44% CR, 36% PR). Of the patients who did not achieve a CR with either CAVE or CEPi, 89% responded to TRT (65% CR, 24% PR + REGR). For the 33 patients with limited disease, the median survival time and 2-year survival rate were 16.1 months and 24%, respectively. The corresponding figures for the 25 patients with extensive disease were 9.8 months and 4%, respectively. Eleven of these 25 patients were "downstaged" to "limited disease" with CAVE + CEPi and then received TRT + PCI + CE. Their median survival time and 2-year survival rate were 12.6 months and 9%, respectively. The EP-based regimen CEPi and TRT were able to convert 44 to 65% of patients to a complete response who had failed to do so with non-EP induction chemotherapy. This study supports the use of an EP regimen with TRT as initial therapy for newly diagnosed small-cell lung cancer.
...
PMID:Etoposide-cisplatin and thoracic radiation therapy salvage of incomplete responders to a noncisplatin induction regimen for limited and extensive small-cell carcinoma of the lung. 861 Jun 40

Occurrence of monocytoi B lymphocytes (MBL) in the lymph nodes of patients receiving preoperative chemotherapy for cancer was examined and compared to lymph nodes in controls who had not received chemotherapy. Number of patients receiving and not receiving preoperative chemotherapy were 3 and 10 cases in ovarian cancer, 7 and 11 in testicular cancer, and 22 and 8 in lung cancer, respectively. Chemotherapeutic agents for ovarian, testicular, and lung cancer consisted of cisplatin, Adriamycin, and cyclophosphamide; cisplatin, vinblastine, and bleomycin; and cisplatin, vindesin, and mitomycin, respectively. MBL were defined morphologically as having abundant pale cytoplasm with distinct cell borders and small nucleus. Immunohistochemistry revealed a B-cell nature of these cells, i.e., CD20+ and/or MB-1+ together with negative reactivity for antibodies for T lymphocytes (CD43, CD45RO, OPD4) and macrophages (KP-1, PGM-1). Monocytoid cells in two cases showed a positive reactivity for CD43 together with CD20. The occurrence rate of MBL in patients with ovarian, lung, and testicular cancer receiving and not receiving chemotherapy was 67% (2/3) and 10% (1/10), 59% (13/22) and 75% (6/8), and 43% (3/7) and 9% (1/11), respectively. The occurrence rate in the total patients receiving chemotherapy (56%) was significantly higher than for those not receiving chemotherapy (28%) (P < 0.05). These findings suggest that chemotherapy-induced depressed immune function is causative for the occurrence of MBL in the lymph nodes. MBL might be found more frequently in nodes from patients who have received chemotherapy in certain settings.
...
PMID:Occurrence of monocytoid B lymphocytes in lymph nodes of patients treated by chemotherapy. 869 36

Cross-resistance presents an obstacle in cancer chemotherapy. Cadmium is a potential carcinogen whose exposure has been shown in epidemiological and laboratory experiments to cause lung cancer. Cadmium also induces various forms of resistance in human lung carcinoma cells. This resistance may be shared by antineoplastic agents, which should be a concern for chemotherapy of cadmium-induced lung cancer. In the present study, two subpopulations of human lung carcinoma A549 cells with a different magnitude of resistance to cadmium toxicity were shown to have a parallel resistance to the cytotoxic action of Adriamycin (ADR), an important anticancer drug. Several factors were examined to investigate the mechanism(s) for the cross-resistance, including cellular metallothionein and glutathione (GSH) concentrations, glutathione S-transferase activity, mdr1 expression, and antioxidant enzyme activities including superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Only cellular GSH content was elevated consistently in the cadmium/ADR-resistant cells relative to the cadmium/ADR-sensitive cells. Treatment with buthionine sulfoximine, a specific inhibitor of GSH synthesis sensitized both cell lines to ADR only when the cellular GSH levels were depleted to about 5% of control. This BSO treatment, however, did not affect cell viability. Further study revealed that the cadmium/ADR-resistant cells have a greater capacity in recovery of cellular GSH content following BSO treatment. The results demonstrate that cross-resistance to ADR exists in cadmium-resistant human lung carcinoma A549 cells, and enhanced GSH synthesis capacity, rather than elevated levels of cellular GSH, may be related to this resistance.
...
PMID:Decreased sensitivity to adriamycin in cadmium-resistant human lung carcinoma A549 cells. 911 95

Although small-cell lung cancer (SCLC) represents only 20% of all lung cancer cases in the United States, it is the most lethal subtype. Combination chemotherapy unequivocally offers the best chance for improved survival in SCLC. Either PE (platinum plus etoposide) or CAV (cyclophosphamide, Adriamycin, and vincristine) is a reasonable first-line therapy. Alternating PE with CAV does not appear to be significantly superior to PE or CAV alone. Increasing dose intensity, although sometimes associated with higher response rates, does not appear to significantly improve survival and should not be used outside of a clinical study. Several new agents with novel mechanisms of action show promise in treating SCLC. These include: gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere), topotecan (Hycamtin), and irinotecan (Camptosar). Given the poor survival and response rates in relapsed patients and the chemoresponsiveness of SCLC, patients with newly diagnosed extensive disease should be encouraged to enroll in phase I or II trials. Thoracic radiotherapy confers a small survival advantage in limited-stage SCLC patients. Although prophylactic cranial irradiation does not significantly improve survival, it does reduce central nervous system (CNS) recurrences with minimal long-term sequelae. Surgery should be considered only for: (1) resection of a solitary pulmonary nodule, which must be followed by adjuvant chemotherapy; and (2) resection of an unresponsive chest tumor, which may harbor a non-small-cell lung cancer component.
...
PMID:Small-cell lung cancer: treatment progress and prospects. 959 76

A cisplatin-resistant cell line, SBC-3/CDDP, was established from a human small-cell lung cancer cell line, SBC-3. The SBC-3/CDDP cells were 13.1-fold more resistant to cisplatin than the parent SBC-3 cells. We investigated the cellular changes of this cell line with regard to the development of resistance to cisplatin. The SBC-3/CDDP cells showed various characteristics as follows: a) increased intracellular glutathione and glutathione S-transferase content b) decreased intracellular accumulation of cisplatin, c) increased topoisomerase I activity and the same topoisomerase II activity as the parent SBC-3 cells, and 4) strong cross-resistance to the platinum analogues and mitomycin C, moderate cross-resistance to 7-ethyl-10-hydroxy-camptothecin (SN-38), 4-hydroperoxy cyclophosphamide, etoposide, Adriamycin and methotrexate, and collateral sensitivity to vinca alkaloids and 5-fluorouracil. From these observations, the SBC-3/CDDP cells could be useful as a well characterized cisplatin-resistant cell line, and the resistance pattem in this cell line will give us much information for eradication of cisplatin-resistant tumor cells.
...
PMID:Cisplatin-resistant human small cell lung cancer cell line shows collateral sensitivity to vinca alkaloids. 961 43

We examined the effect of a novel topoisomerase I and II (topo I and II) inhibitor, TAS-103, on P-glycoprotein (P-gp)-expressing and -nonexpressing drug-resistant human small-cell lung cancer (SCLC) cells in vitro and in vivo. We observed that TAS-103 was effective in inhibiting in vitro proliferation of human SCLC (SBC-3 and H69) cells and their drug-resistant variants SBC-3/ADM or SBC-3/CDDP and H-69/VP, respectively. SBC-3/ADM and H-69/VP expressed high P-gp, whereas SBC-3/CDDP did not. TAS-103 also effectively reduced the tumor growth (more than 50% inhibition) of the parental as well as MDR SCLC cells grown SC in nude mice. Adriamycin (ADM) and cisplatin (CDDP), on the other hand, were effective only against the parental cells, while these drugs failed to inhibit the respective drug-resistant variants in vitro or in vivo. TAS-103 was observed to induce apoptosis dose dependently in the parental as well as drug-resistant SCLC cells as analyzed after 48 h of in vitro treatment, suggesting that the stabilization of cleavable topo I- or II-DNA complexes by topo I and II inhibitors like TAS-103 is followed by apoptosis of the cells. Overall, our study suggests that TAS-103 may have clinical application against drug-resistant human SCLC.
...
PMID:Therapeutic efficacy of a new topoisomerase I and II inhibitor TAS-103, against both P-glycoprotein-expressing and -nonexpressing drug-resistant human small-cell lung cancer. 1060 16

Recent evidence indicates that individuals with a p53 germ-line mutation (Li-Fraumeni syndrome) have a 50% risk of developing lung cancer by age 60. In this study, p53 heterozygous knockout mice and p53 transgenic mice carrying a dominant negative mutant were crossed with the A/J mouse, which is highly susceptible to lung tumor induction, to investigate whether a p53 germ-line mutation is a predisposing gene for carcinogen-induced pulmonary adenomas in mice. The number of lung tumors was not significantly increased in (TSG-p53 x A/J)F1 p53 heterozygous knockout mice as compared with that in (TSG-p53 x A/J)F1 wt mice 16 weeks after exposure to N-nitrosomethylurea (MNU). In contrast, an average of 22 lung tumors were observed in (UL53-3 x A/J)F1 mice carrying a mutant p53 transgene (135Valp53) compared with an average of 7 lung tumors seen in (UL53-3 x A/J)F1 wt mice after treatment with N-nitrosomethylurea. Similar enhancement of lung tumor multiplicity (approximately 3-fold) was seen when mutant versus wt mice were treated with the tobacco-related carcinogens benzo[a]pyrene or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. These results suggest that the mutant p53 transgene may have a dominant negative effect on the wt p53. The potential usefulness of this new mouse model in lung cancer chemoprevention and chemotherapy was examined. The chemopreventive efficacy of the green tea or a combination of dietary dexamethasone and myoinositol and the chemotherapeutic efficacy of Taxol or Adriamycin was examined in wt mice or mice with a mutation in the p53 gene. Mice treated with dexamethasone/myo-inositol and green tea displayed an average of 70 and 50% inhibition of lung tumors, respectively, regardless of p53 status. Similarly, when mice bearing established lung adenomas were treated with Taxol or Adriamycin, a decrease in tumor volume of approximately 70% was observed independent of p53 mutation status. Thus, the (UL53-3 x A/J)F1 p53 transgenic mouse seems to be an excellent model for human carriers of p53 germ-line mutations (Li-Fraumeni syndrome). Furthermore, the lung adenomas generated in this model possess mutations in both the K-ras proto-oncogene and the p53 tumor suppressor gene. This model should prove directly useful for chemoprevention and chemotherapy studies.
...
PMID:A germ-line p53 mutation accelerates pulmonary tumorigenesis: p53-independent efficacy of chemopreventive agents green tea or dexamethasone/myo-inositol and chemotherapeutic agents taxol or adriamycin. 1070 3

The tumor suppressor gene p53 is perhaps the most commonly mutated gene in human cancer, being mutated in a high percentage of colon, breast, skin, bladder, and many cancers of the aerodigestive tract. Individuals with Li-Fraumeni syndrome, who routinely have a germline mutation in the p53 tumor suppressor gene, are at high risk for lung cancer, confirming its intimate role in lung tumorigenesis in humans. In contrast, the majority of chemically induced or spontaneous cancers in rodents do not contain mutations in p53. Therefore, we examined a transgenic mouse that contains a dominant negative mutation (Arg135Val) in the p53 gene placed under the control of its own endogenous promoter. The resulting mice have 3 copies of the mutated transgene as well as 2 normal p53 alleles. In the chemical carcinogenesis studies, we employed mice containing the mutated p53 gene to examine for carcinogen susceptibility. We found that mice with the p53 mutation, on an A/J F1 background, were more susceptible to a number of potential lung carcinogens, including N-methyl-N-nitrosourea (MNU) and the known tobacco carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(a)pyrene (BP). Mice with a mutant p53 developed larger tumors and roughly 3 times as many tumors, emphasizing the potential effects of a p53 mutation both on tumor initiation and progression. In addition, we examined 2 nonlung carcinogens, 1,2-dimethylhydrazine (DMH), a colon carcinogen, and N-butyl-N-(4-hydroxybutyl)-nitrosamine (OHBBN), a bladder carcinogen. Interestingly a germline p53 mutation increased the incidence of DMH-induced colon, lung, hepatic, and uterine tumors, while having limited effects on OHBBN-induced bladder tumors. Because of its heightened susceptibility we are examining the use of this model in smoke-induced tumorigenesis in A/J mice as well. Employing the lung adenomas induced by NNK, we found that mice with or without a p53 mutation were equally susceptible to the chemopreventive effects of dexamethasone plus myo-inisitol and green tea. These tumors, which arise in a highly reproducible manner in p53 transgenic mice following carcinogen treatment, have mutations in both p53 and the K-ras oncogene. Thus, this model appears useful for examining for potential chemotherapeutic agents. p53-mutated or wild-type mice were equally susceptible to the therapeutic effects of Taxol or Adriamycin. Interestingly, piroxicam was similarly effective in inhibiting colon tumor formation by DMH in mice with or without a mutation in the p53 tumor suppressor gene. In contrast, lung and uterine tumors developing in these mice were not susceptible to the chemopreventive effects of piroxicam. In summary, mice with mutations in the p53 tumor suppressor gene appear to be particularly applicable for basic mechanistic studies, for screening for potential carcinogens, and for screening for chemopreventive or chemotherapeutic agents.
...
PMID:Use of p53 transgenic mice in the development of cancer models for multiple purposes. 1119 57

Acquired anticancer drug resistance in cancer cells is often a result of an increase in levels of the ATP binding cassette (ABC) transporters that export anticancer drugs from cancer cells, suggesting that anticancer drugs may induce genes that mediate drug resistance in cancer cells. In this study, the induction of anticancer drug transporter gene expression by Adriamycin was examined in human lung cancer cell lines. Increased expression of MDR1, MRP5 and SMRP mRNA was observed 48 hr after the initiation of Adriamycin exposure in human lung cancer PC-14 cells and cisplatin-resistant PC-14/CDDP cells, in a dose-dependent manner as measured by TaqMan real-time RT-PCR. The levels of MRP-1, MRP2 and LRP mRNA were not altered by Adriamycin exposure. The biologic functions of the MRP5 and SMRP genes have not been fully clarified. To elucidate the relationship between Adriamycin resistance and MRP5 and SMRP, mRNA levels of MRP5 and SMRP in Adriamycin-resistant cell lines were compared with the parental cells. Increased expression of MRP5 and SMRP mRNA was observed in all 3 cell lines (SBC-3/ADM, AdR MCF7 and K562/ADM) by Northern blot analysis and RNase protection assay. These results suggest that subacute exposure of lung cancer cells to Adriamycin induced MRP5 and SMRP and that long-term exposure with Adriamycin selected the MRP5- and SMRP-overexpressing lung cancer cells. MRP5 and SMRP is a candidate molecule for acquired Adriamycin resistance in addition to MDR1.
...
PMID:Induction of MRP5 and SMRP mRNA by adriamycin exposure and its overexpression in human lung cancer cells resistant to adriamycin. 1174 26

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