Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gnidimacrin, a diterpene compound, isolated from the methanol extract of Stellera chamaejasme L, showed significant antitumor activities against mouse leukemia P-388 and L-1210 in vivo. At the dosages of 0.02-0.03mg/kg ip, the in increase in life span (ILS) was 70% and 80%, respectively. Gnidimacrin was also active against murine solid tumors in vivo, such as Lewis lung carcinoma, B-16 melanoma and colon cancer 26. It showed ILSs of 40%, 49% and 41% at the dosages of 0.01-0.02mg/kg ip, respectively. Gnidimacrin strongly inhibited cell proliferation of human cancer cell lines such as leukemia K562, stomach cancers Kato-III, MKN-28, MKN-45, and mouse L-1210 by the MTT assay and colony forming assay in vitro. The IC50 of gnidimacrin was 0.007-0.00012microgram/ml. It is concluded that gnidimacrin is the principal antitumor element in Stellera chamaejasme L. with strong antitumor activities.
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PMID:[The antitumor activities of gnidimacrin isolated from Stellera chamaejasme L]. 765 81

A multi-institutional cooperative group trial was undertaken by the Cancer and Leukemia Group B (CALGB) to evaluate the efficacy of the combination of cisplatin and intravenous etoposide for the treatment of metastatic or recurrent non-small cell lung cancer (NSCLC). The doses used were those previously determined to be the maximally tolerated dose of this drug combination. Forty patients were entered into the trial, 37 of whom were eligible for evaluation. Cisplatin (35 mg/M2/day for 3 days) and etoposide (200 mg/M2/day for 3 days) were administered every 28 days for a planned 6 cycles of therapy. Sixteen of 37 evaluable patients (43%) responded to therapy. Myelosuppression was the dominant toxicity, with 89% of the patients experiencing grade 4 neutropenia, and nearly half grade 3 or 4 thrombocytopenia. Median survival was 8.5 months, with 30% of the patients alive at 1 year and 10% alive at 2 years. Malaise, fatigue, and peripheral neuropathy were the other major toxicities. The combination of etoposide at the dose of 200 mg/M2/day for 3 days and cisplatin at 35 mg/M2/day for 3 days is a highly potent combination against metastatic non-small cell carcinoma.
Lung Cancer 1995 Dec
PMID:Etoposide (VP-16) and cisplatin at maximum tolerated dose in non-small cell lung carcinoma: a Cancer and Leukemia Group B study. 871 68

Based on previously published observations regarding the protective effects of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) against gamma radiation, alkylating agents and ultraviolet radiation, we hypothesized that the protection against such DNA damaging treatments can be the result of a 'stress'-like response induced by these cytokines and mediated by early response cellular gene(s). By applying the mRNA differential display to RNA obtained from A549 lung carcinoma cell line that was incubated with 50 ng/ml IL-1 for 0, 1, 2, and 6 h, we identified several cDNA fragments that correspond to genes regulated by IL-1. The full length cDNA for one fragment was obtained using 5'RACE, cloned, sequenced, and found to be homologous to human A1, a Bcl-2-related gene. In this study, we report that the expression of human A1 is either absent or present at low levels in leukemic cells, while it is expressed in human bone marrow cells and abundant in peripheral blood progenitors. It is induced by IL-1 and TNF alpha in A549 lung carcinoma, bone marrow, and certain leukemic cells. A1 is also induced in leukemic cells during granulocytic or macrophage but not erythroid differentiation. In conclusion, this is the first demonstration that A1 is inducible by cytokines in human bone marrow and certain tumor cells as well as myeloid differentiation in leukemic cells.
Leukemia 1997 Jul
PMID:Human A1, a Bcl-2-related gene, is induced in leukemic cells by cytokines as well as differentiating factors. 920 81

Our recent studies using various costimulatory molecules have demonstrated that antitumor effect could be induced by B7- or B70-transduced mouse tumors. To augment antitumor effect in vivo, the combination therapy with a costimulatory gene and a cytokine, interkeukin 12 (IL-12), gene to treat metastatic mouse lung tumor was investigated. We transfected with mouse B7 and/or IL-12 into mouse lung carcinoma 3LL, and three transfectants (IL-12/3LL, B7/3LL and IL-12/B7/3LL) were generated. CTL activity induced by the inoculation of IL-12/B7/3LL was increased about 10-fold compared with parental 3LL inoculation. We then examined the therapeutic efficacy of combination with B7 and IL-12-transduced tumors. Four weeks after 3LL inoculation, lung metastasis was significantly reduced by IL-12/B7/3LL post-inoculation, indicating that potent therapeutic antitumor immunity can be induced by combination with costimulators B7 and IL-12. Recently, it was reported that p40 subunit of IL-12 appeared to be a specific inhibitor for IL-12 heterodimer in vitro. To clarify the biological functions of p40 in vivo, we generated the myoblast transfectants which produced IL-12 p40 alone. Local production of IL-12 p40 from transfectant could suppress allogenic CTL induction and Th1-type antibodies (IgG2a/2b/3) production in vivo. Furthermore, IL-12 p40 producing myoblast are less susceptible to rejection compared with parental myoblast, indicating that IL-12 p40 gene transfer may be useful therapeutically in Th1-mediated transplantation and autoimmune disorders.
Leukemia 1997 Apr
PMID:Immunoregulation by B7 and IL-12 gene transfer. 920 58

In a prior Cancer and Leukemia Group B (CALGB), 16% of a small cohort of patients with extensive small call lung cancer who had failed to obtain a complete remission with chemotherapy did obtain a complete remission after therapy with interleukin-2 (IL-2). In this current trial, 10 patients with extensive small cell lung cancer who had had no prior therapy were treated with subcutaneous IL-2 as induction therapy and then standard chemotherapy with etoposide/cisplatin. Only one patient experienced an objective response to the IL-2 administered prior to chemotherapy. The factors governing response to IL-2 in the first trial but not in this trial are discussed.
Lung Cancer 1998 Jan
PMID:Subcutaneous interleukin-2 as initial therapy for patients with extensive small cell lung cancer: a phase II trial of Cancer and Leukemia Group B. 949 37

Several studies have suggested that biochemical or molecular markers examined in non-small cell lung cancer carry prognostic or treatment response information. Non-small cell lung cancer patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of HER2 (c-erbB-2), a membrane-bound receptor with tyrosine kinase activity, has been associated with shortened survival. The Cancer and Leukemia Group B (CALGB) performed a study of patients with stage IIIA (N2 nodes positive) non-small cell lung cancer in which patients received initial chemotherapy followed by surgery, then post-operative therapy consisting of sequential chemotherapy and radiation therapy. Since all patients underwent mediastinoscopy, this provided an opportunity to compare pre- and post-chemotherapy tumor specimens to test the hypothesis that these proteins would predict treatment response. In particular, we hypothesized that the post-chemotherapy specimens would be enriched for NE marker negative cells because of the increased sensitivity of NE positive cells to chemotherapy. We performed immunohistochemical analysis for a panel of NE markers [neuron-specific enolase (NSE), Leu-7, chromogranin A (ChrA), synaptophysin (Syn)], HER2 and CEA to determine if there was an effect of therapy on the percentage of cells expressing these markers. Secondary endpoints were a correlation with chemotherapy response and survival. Slides were scored for intensity (0-4) and percentage of cells positive (0-4). Of 61 eligible patients, there were 38 with both pre- and post-chemotherapy specimens. When both intensity of staining and percentage of positive cells were considered, post-chemotherapy specimens had a higher percentage of positive NE markers compared with pre-chemotherapy. In addition, there was no correlation between NE marker, HER2 or CEA expression (prior to or post treatment) and response to chemotherapy or survival. These data do not support the hypothesis that NE positive tumor cells are preferentially killed by chemotherapy in patients with stage IIIA non-small cell lung cancer.
Lung Cancer 1998 Sep
PMID:Analysis of neuroendocrine markers, HER2 and CEA before and after chemotherapy in patients with stage IIIA non-small cell lung cancer: a Cancer and Leukemia Group B study. 985 98

In order to explore non-cisplatin containing regimens for advanced non-small cell lung cancer, Cancer and Leukemia Group B conducted a randomized Phase-II study of two novel combinations, paclitaxel/ifosfamide and vinorelbine/ifosfamide. Both regimens were active with a 38% response rate (95% CI: 24%, 53%) and 31% (95% CI: 18%, 47%), respectively. Median survivals were 8.5 and 7.4 months. Toxicity, mostly neutropenia, was acceptable. These two combinations establish a 'proof of principle' that non-cisplatin containing regimens also have activity in this setting.
Lung Cancer 2000 Apr
PMID:Paclitaxel/ifosfamide or navelbine/ifosfamide chemotherapy for advanced non-small cell lung cancer: CALGB 9532. 1070 11

Several studies have suggested that non-small cell lung cancer (NSCLC) patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of p53 and HER2 may confer relative chemotherapy resistance and shortened survival. The Cancer and Leukemia Group B performed a series of studies involving sequential chemotherapy followed by radiation for patients with unresectable stage III NSCLC. The objectives of this study were to analyze pathological specimens using immunohistochemistry for NE markers, p53 and HER2 to determine if there was a correlation between marker expression and response or survival. Of 160 eligible patients, 28 (18%) were not evaluable because of inadequate material. The percentage of specimens positive for markers was as follows: neuron-specific enolase 38%, Leu-7 2%, chromogranin A 0%, synaptophysin 5%, > or =2+NE markers 3%, p53 61%, and HER2 65%. There was no statistically significant correlation between any individual marker and response to induction chemotherapy or response to combined chemotherapy/radiation except for synaptophysin. Six of 6 (100%) synaptophysin positive tumors responded by the completion of all therapy compared with 69/125 (55%) synaptophysin negative tumors (P=0.04). None of the individual markers had a significant effect on survival in univariate analysis. Neuron-specific enolase was marginally significant in multivariate analysis (P=0.08). In conclusion, this study did not demonstrate that expression of NE markers, p53 and HER2 were predictive of response to chemotherapy, combined chemotherapy/radiation or for survival in this group of patients with stage III NSCLC. Future studies must employ either different markers or be performed on more adequate surgical specimens.
Lung Cancer
PMID:Use of neuroendocrine markers, p53, and HER2 to predict response to chemotherapy in patients with stage III non-small cell lung cancer: a Cancer and Leukemia Group B study. 1155 6

Doxorubicin is the most widely studied agent for the treatment of malignant mesothelioma. In conventional doses, the response rate is approximately 17%. Higher dose doxorubicin has been successfully employed in other tumor types. Dexrazoxane has been demonstrated to reduce the cardiac toxicity associated with long term, chronic use of doxorubicin. Based upon phase I data generated by the Cancer and Leukemia Group B (CALGB) indicating that doxorubicin at a dose of 120 mg/m(2) when combined with dexrazoxane and GM-CSF could be safely administered, the CALGB undertook a phase II study of high-dose doxorubicin in patients with malignant mesothelioma. Toxicity was excessive, necessitating protocol modification and ultimately protocol termination. There were no objective responses observed. We conclude that high-dose doxorubicin administered with dexrazoxane is unacceptably toxic in this patient population.
Lung Cancer 2001 Nov
PMID:High-dose doxorubicin, dexrazoxane, and GM-CSF in malignant mesothelioma: a phase II study-Cancer and Leukemia Group B 9631. 1167 88

To evaluate the frequency and cytogenetic and immunophenotypic features of therapy-related, precursor B-cell acute lymphoblastic leukemia (ALL), 152 cases of immature B-cell ALL were reviewed. These were compared to the frequency of therapy-related acute myeloid leukemia (t-AML) during the same time period. Eight ALL cases with a prior diagnosis of malignancy were identified, including six (4.0%) with prior therapy considered to be therapy-related ALL (t-ALL). The t-ALL cases followed treatment for breast carcinoma (two cases), lung carcinoma (two cases), lymphocyte predominance Hodgkin's disease and follicular lymphoma with a latency period of 13 months to 8 years. All t-ALL cases had a pro-B (CD10-negative) immunophenotype with significantly higher expression of CD15 and CD65, compared to the de novo CD10-positive ALL cases. All six t-ALL cases had MLL abnormalities by fluorescence in situ hybridization, and four showed t(4;11)(q21;q23). These represented half of all 11q23-positive adult ALL cases. During the same time period, 4.9% of all AML cases were considered t-AML. There was a 16.7% frequency of 11q23 abnormalities in the t-AML group. Despite the similar frequency in therapy-related disease among ALL and AML cases, there were differences in the frequency of the diseases and t-ALL represented 12% of all therapy-related leukemias. However, t-ALL represented 46% of all 11q23-positive therapy-related leukemias. The immunogenetic features of t-ALL appear distinct and may aid in identifying more cases of this disease type in the future.
Leukemia 2003 Jun
PMID:High frequency of pro-B acute lymphoblastic leukemia in adults with secondary leukemia with 11q23 abnormalities. 1276 73


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