Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007131 (non-small cell lung cancer)
 22,601 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.
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PMID:Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. 172 Mar 82

A general transcription factor IID which binds to the TATA box promoter element on RNA polymerase II genes regulates and initiates eukaryotic mRNA synthesis. A quantitative polymerase chain reaction procedure was developed and the human transcription factor IID (hTFIID) transcript was measured in normal human tissues, lung carcinomas, lung carcinoma cell lines, and breast carcinomas. In some normal tissues such as liver, fetal lung, and placenta, relatively low to moderate levels of hTFIID mRNA were detected. In contrast, hTFIID transcript was highly expressed in nearly all solid lung carcinomas and cell lines including both small cell lung cancer and non-small cell lung cancer. hTFIID mRNA was present to a greater extent in small cell lung cancer than non-small cell lung cancer in solid tumors and cell lines. In solid carcinomas of breast, overexpression of hTFIID was also detected. A serum induction study using a serum-starved small cell lung cancer cell line, Lu134BS, indicated hTFIID transcription to be rapidly induced at 15 min following stimulation and its response essentially similar to that of protooncogene, c-fos. These results indicate the involvement of the expression of the general transcription factor hTFIID in lung and breast carcinoma, such as being associated with poor differentiation and high mitotic activity.
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PMID:A general transcription initiation factor, human transcription factor IID, overexpressed in human lung and breast carcinoma and rapidly induced with serum stimulation. 172 4

Carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and creatine kinase-BB (CK-BB) were estimated in blood serum of 75 patients with primary lung carcinoma and of 20 patients with nonmalignant lung diseases. CEA and NSE were determined by immunoenzymatic method using monoclonal antibodies (Abbott CEA-EIA and Roche NSE-EIA) and CK-BB was assayed using kits supplied by Boehringer-Mannheim (Monotest CK-NAC aktiviert). Enhanced levels of CEA were observed in 64% of patients with lung carcinoma, mainly with adenocarcinoma. Increased activities of NSE and CK-BB were obtained in 47% and 39% of patients, respectively, principally of those with small cell carcinoma. The CEA level was dependent on the stage of advanced NSCLC carcinoma and of NSE and CK-BB on the stage of advanced SCLC carcinoma. The complex analysis of the three markers has given 100% specificity of test.
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PMID:Carcinoembryonic antigen, neuron-specific enolase and creatine kinase-BB as tumor markers for carcinoma of the lung. 176 88

Two monoclonal antibodies (mAb), termed ED6 and LD6, were obtained by immunizing mice with cytotoxic T cell lines expressing the T cell receptor (TcR) gamma/delta. These mAb were selected according to their ability to trigger the cytolytic program of the immunizing cell lines in a redirected killing assay. Both mAb recognized molecule(s) expressed on the surface of most long-term cultured TcR gamma/delta +, TcR alpha/beta + and CD3-CD16+ lymphocytes, while it was absent on resting peripheral blood lymphocytes. In addition both mAb reacted with neoplastic B cell lines, Epstein-Barr virus-transformed B cell lines, small cell lung cancer and glioma cell lines, while no surface reactivity was detected on ovarian, breast, colon and non-small cell lung cancer lines. The functional activity of these mAb was studied by two cytolytic assays. Both mAb were able to trigger the cytolytic program of CD3+TcR gamma/delta + polyclonal cell lines and of a CD3-CD16+ NK cell clone against the murine mastocytoma target cell line P815 (Fc receptor+) in a 4-h 51Cr-release assay. In addition, ED6 and LD6 hybridomas were lysed by TcR gamma/delta + effector cells while other hybridomas (obtained from the same fusion) were not lysed. ED6 and LD6 mAb (in the presence of submitogenic doses of the phorbol 12-myristate 13-acetate) also induced the secretion of interleukin 2 by ED6/LD6+ T cell clones expressing TcR gamma/delta or alpha/beta. mAb-induced surface antigen modulation experiments showed that the antigenic determinant recognized by ED6 and LD6 co-modulated, thus indicating that the two mAb probably recognize the same or closely associated molecules. The molecular characteristics of the antigen recognized by the mAb were investigated by Western blot analysis. The LD6 mAb recognized a major band of approximately 65 kDa, both under nonreducing and reducing conditions. These data indicate that ED6 and LD6 mAb recognize a novel non-lineage-specific activation antigen which is involved in the induction of the functional program of long-term cultured T or natural killer cells.
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PMID:A novel surface molecule expressed by long-term cultured T and natural killer cells is involved in cell activation. 183 83

The establishment of reliable preclinical test is essential for the reasonable clinical trial. As a methodology for the screening of new active anticancer agents, disease oriented strategy using human tumor cell lines has been proposed in USA. The important questions in DOS are to determine the representative cell lines of specific cancer and it is also extremely important to decide the numbers of cell lines used for the screening. CPT-11, topoisomerase I inhibitor, developed in my country has been demonstrated to be active against lung cancer cell lines compared with mice tumors such as S-180 and P-388. However, no compound is demonstrated to be clinically active so far by this methodology. The criteria for the application of clinical trial are obscure and each drug company decides empirically by themselves. We have proposed to use PEI (predictive efficacy index) for the prediction of antitumor activity of new compounds. The clinical effect of new platinum analogue well correlated with this value. We have conducted phase II trial of 5-FU + LV against NSCLC without no prior chemotherapy. No responder was observed in the trial. Augmentive effect of leucovorin on the cytotoxicity of 5-FU and FdUrd was examined in vitro against NSCLC and colon cancer cell lines. Leucovorin stimulated the cytotoxicity of both drugs only against colon cancer cell lines. We tried to predict the response rate of new platinum derivative based on the data of bioassay of patient's serum administrated with platinum compounds. The predicted response rates of 254-S were 57-67% and 16-27% against SCLC and NSCLC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Preclinical trials from the standpoint of clinical trials]. 185 17

Platelet counts were evaluated in 714 patients with advanced non-small cell lung cancer (N-SCLC), small cell carcinoma of the lung (SCCL), and colon cancer entered to a clinical trial. Patients had not received prior chemotherapy. Platelet counts were not different in patients who had received radiation therapy prior to entry to the study. In comparison to the other tumor types, patients with N-SCLC demonstrated an increased prevalence of thrombocytosis (counts greater than 400,000/mm3), higher platelet counts at the time of entry to the study, higher over all mean platelet counts, relative preservation of high platelet levels during disease progression, and no relationship between platelet numbers and the amount of chemotherapy given. By contrast, platelet counts in patients with SCCL were negatively correlated with the absolute amount of cyclophosphamide and adriamycin given, and declined most dramatically with disease progression and death. Platelet numbers did not correlate with fibrinopeptide A or fibrin split product levels suggesting that disseminated intravascular coagulation or fibrinolysis may have had less influence on platelet numbers than certain other factors. By contrast, significant correlations were found for all three tumor types between platelet numbers and other indicators of bone marrow function including anemia, total leukocyte count, and absolute neutrophil count; and the fibrinogen level. Based upon these findings, we postulate that the host response to malignancy, possibly in the form of production of bone marrow-stimulating cytokines, may play a prominent role in regulation of platelet counts in these (and perhaps other) neoplasms, and that a particularly prominent and persistent degree of marrow stimulation exists in patients with N-SCLC.
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PMID:The platelet count in carcinoma of the lung and colon. 196 50

Between January 1981 and December 1989, a total of 205 patients with lung cancer were treated in different multicenter trials in our hospital. In 130 cases, small cell lung cancer (SCLC), and in 75 cases, non-small cell lung cancer (NSCLC) was diagnosed. Abdominal sonography for pretreatment staging revealed liver metastasis in 59 patients (42 SCLC, 17 NSCLC), sonographic patterns of liver metastasis were described and the prognostic significance of evaluation of response according to abdominal ultrasound after the first two cycles of treatment was investigated. For both histological types of lung cancer, the hypoechoic or isoechoic (80%), small noduled (97%) liver metastasis with multifocal spread (86%) was found to be typical. Sonographic follow-up examinations for liver metastasis were performed in 46 patients (35 SCLC, 11 NSCLC), and 134 chemotherapy cycles. Response to chemotherapy according to abdominal ultrasound was seen in only 3 out of 11 patients with NSCLC (27%) and 17 out of 35 with SCLC (49%). Best response was achieved after the first two cycles with only 6 patients (6 SCLC, 0 NSCLC) exhibiting complete liver metastasis remission. All other patients exhibited on ultrasound a progressive or non-responsive illness. In summary, sonography is reliable with respect to the diagnosis and follow-up examination of liver metastases in lung cancer. A lack of metastasis regression subsequent to the first two cycles of therapy is associated with poor prognosis and continued treatment cannot be justified in such patients.
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PMID:Prognostic value of response to chemotherapy using ultrasound in lung cancer with metastatic liver involvement. 196 23

Lung cancer patients with poor late prognosis should receive adjuvant chemotherapy. Its application in non-small cell lung cancer (NSCLC) is only justified in clinical studies, since there is no evidence of its efficacy. In small cell lung cancer (SCLC) chemotherapy is supplemented by local therapy regimens like radiotherapy and/or surgery. At present clinical studies are examining whether chemotherapy should be applied before or after surgical treatment.
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PMID:[Bronchial cancer--adjuvant chemotherapy]. 198 75

Etoposide is an important drug that has been recently incorporated with other agents in the curative treatment of patients with advanced neoplasms, including germ cell tumors, non-Hodgkin's lymphomas (NHL), and small cell lung cancer (SCLC). Etoposide demonstrates remarkable schedule dependency. A randomized comparison has shown an impressive survival difference for patients with extensive SCLC receiving a 5-day course versus those receiving a 1-day course. Because of these and previous clinical and laboratory data, etoposide is now given intravenously or orally in a 3-day to 5-day schedule. It is generally accepted that approximately 50% of the orally administered drug is absorbed. The authors have initiated several etoposide studies using an extended administration schedule, believing that a prolonged schedule may be superior to the standard 3-day to 5-day schedule. This was initially tested in a Phase I study. Results showed that etoposide (50 mg/m2/d) given over 21 days was feasible and was associated with only moderate toxicity. Several Phase II studies have been completed or are nearing completion, including studies in patients with SCLC, NHL, germ cell tumors, soft tissue sarcoma, renal carcinoma, and ovarian carcinoma. Responses have been seen in all of these groups, particularly in patients with SCLC, lymphoma, and germ cell tumors. In these groups we saw responses in patients who were clearly resistant to etoposide plus cisplatin given in a standard schedule or in some patients who were resistant to high-dose etoposide with bone marrow transplantation. Investigators at Indiana University Medical Center who studied oral etoposide in a similar fashion in patients with advanced germ cell tumors and SCLC achieved results similar to those reported here. The authors have initiated a number of combination chemotherapy programs using the chronic oral form of etoposide. These include patients with SCLC, non-small cell lung cancer, and elderly patients with high-grade and intermediate forms of NHL. In addition, chronic intravenous oral etoposide is being used in salvage approaches for patients with acute myelocytic leukemia and recurrent resistant intermediate-grade and high-grade NHL. Preliminary pharmacokinetic data suggest that a 50-mg/m2 oral dose is highly bioavailable (91% to 96%). Therefore, during a prolonged oral course at 50 mg/m2, many patients maintain a minimum plasma concentration of 1 microgram/ml. Further studies of multiple dose or continuous infusion etoposide to maintain a potentially critical plasma level are in progress. Etoposide administered in this way could represent a "new" drug because many of its features are different, and its activity spectrum may be broader.
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PMID:Chronic oral etoposide. 198 32

The lamins, an intranuclear class of intermediate filament proteins, are major structural proteins of the nuclear envelope. In the present study, the three abundant mammalian lamins (lamins A, B, and C) were observed to be present in roughly equivalent amounts in the Calu-1, Calu-3, H157, and SK-MES-1 non-small cell lung cancer lines. In the small cell lung cancer lines OH-1, OH-3, NCI-H82, NCI-H209, and NCI-H249, levels of lamin B were similar to those observed in the non-small cell lines, but the levels of lamins A and C were diminished by greater than or equal to 80%. The relationship between lung cancer phenotype and lamin expression was explored further in the NCI-H249 small cell line. Introduction of the v-rasH oncogene into this line gives rise to a cell line (NCI-H249rasH) with many features of large cell carcinoma of the lung (Falco, J. P., Baylin, S. B., Lupu, R., et al. J. Clin. Invest., 85: 1740-1745, 1990). Concomitant with the v-rasH-induced change in phenotype, a greater than 10-fold increase in the amounts of lamins A and C was observed. Levels of the cytoplasmic intermediate filament protein vimentin also increased. In contrast, levels of a variety of nonlamin nuclear polypeptides including topoisomerase I, topoisomerase II, poly(ADP-ribose) polymerase, and the nucleolar protein B23/nucleophosmin did not change. Comparison of polyadenylated RNA from NCI-H249 and NCI-H249rasH cells on Northern blots revealed similar levels of the mRNA for lamin B but higher levels of the mRNAs for lamins A and C in the v-rasH-expressing cell line. These observations provide evidence for differences in nuclear envelope structure in histologically different neoplastic cells derived from the same epithelial cell system and suggest that differences in lamina structure result from phenotype-specific differences in lamin gene expression.
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PMID:Differential expression of nuclear envelope lamins A and C in human lung cancer cell lines. 198 76


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