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

We have examined the distribution of ras p21 oncoprotein expression in cytologic specimens from 73 primary bronchial carcinomas using an immunocytochemical analysis. The cytologic preparations studied represent the two major groups of histological types of lung cancer: Small Cell Lung Carcinoma (SCLC) and Non-Small Cell Lung Carcinoma (NSCLC) (squamous cell carcinoma and adenocarcinoma). The differential expression of ras p21 oncoprotein correlated with histological classification and was found in 30% of 23 small cell lesions, 61% of 28 squamous cell lung carcinomas and 32% of 22 adenocarcinomas. The ras p21 oncoprotein was commonly expressed in NSCLC cases (48%) as compared to SCLC cases (30%).
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PMID:Immunocytochemical study of RAS oncoprotein in cytologic specimens of primary lung tumours. 216 47

A Phase II trial of carboplatin (CBDCA) was performed in 33 patients with advanced lung cancer, including 15 patients with inoperable Stage III non-small-cell (NSCLC) and 18 patients with relapsed small-cell (SCLC) lung cancer. Initial dosage was 320 mg/m2 infused over 24 h; in the absence of hematologic toxicity, subsequent doses were escalated to 400 mg/m2. Patients received a median of two cycles (range 1-13 for NSCLC and 1-5 for SCLC) of therapy. There were no complete or partial responses among the NSCLC patients. Among the SCLC patients, two had a partial response. In vitro analysis of the cytotoxicity of CBDCA and its parent compound cisplatin by two different methods for 20 NSCLC cell lines suggested that equivalent tumor cell kill is achieved by the two compounds, but this occurs at a log lower concentration of cisplatin than of CBDCA. The in vitro cytotoxicity against NSCLC of CBDCA at a concentration predicted to be in the range produced by the dose employed in this Phase II study correlated well with the resulting very modest in vivo benefit. In vitro, a continuous dose-response relationship exists for CBDCA, suggesting that if higher doses could be administered safely to patients, greater clinical benefit might occur. We conclude that single agent CBDCA in the dosage and schedule administered has less than 20% activity (95% confidence intervals 0-19%) in NSCLC and an 11% response rate in SCLC (95% confidence intervals 2-34%). Despite this outcome, in vitro data in human NSCLC cell lines suggest higher dosages should perhaps be evaluated before discounting a role for CBDCA in the management of NSCLC.
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PMID:A phase II trial of carboplatin (CBDCA) in small-cell and non-small-cell lung cancer with correlation to in vitro analysis of cytotoxicity. 216 37

From 1970 through 1987, 77 patients with Stage I lung cancer were treated with definitive radiation therapy (RT) alone at the Fox Chase Cancer Center or the Hospital of The University of Pennsylvania. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidates for surgical resection because of premorbid medical problems or patient refusal. The median age was 72 years, although 10 patients were over 80. The histologic cell type was squamous in 44, adenocarcinoma in 15, large cell in 3, adenosquamous in 1, non-small cell in 11, and bronchioli-alveolar in 3. Tumor size was retrievable in 75 patients and 25 were less than or equal to 3 cm, 41 from 3-6 cm, and 9 greater than 6 cm. Diagnostic staging varied during the study period. Twelve patients, evaluated with a CT scan of the chest, including the liver, and a bone scan were classified as having "excellent" staging, 24 patients with conventional tomography, liver-spleen scan and a bone scan had "good" staging, and 41 patients were staged less rigorously. The RT was of megavoltage energy in all patients. The median dose was 60 Gy. The mediastinum was treated in all but eight patients who had poor pulmonary function. Survival was measured from the date of pathologic diagnosis. The actuarial 3-year survival rate of the entire group of patients is 17% with a median survival time of 20 months. Of the 61 deaths, 51 were due to disease and 10 were due to intercurrent disease without evidence of tumor recurrence. The actuarial 3-year disease-specific survival (DSS) was 22%. The 3-year disease-specific survival for patients with tumors less than 3 cm and from 3-6 cm was 30% and 17%, respectively. All nine patients with tumors greater than 6 cm were dead of disease. Local progression occurred in 33 patients, resulting in a 44%, 3-year actuarial freedom from local progression. The median time to local failure was 28 months and there were no local failures after 3 years in the 18 patients eligible for observation beyond this point. Of the patients with "excellent" staging, only 2 of 12 were dead of disease compared with 22 of 24 with "good" staging and 30 of 41 of the remainder. In this large group of Stage I non-small cell lung cancer, thorough pre-treatment staging and smaller tumor size are associated with a more favorable outcome.
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PMID:The influence of tumor size and pre-treatment staging on outcome following radiation therapy alone for stage I non-small cell lung cancer. 216 20

Five-year survival rates for patients with non-small cell lung cancer have changed only minimally over the past 20 years. Although systemic chemotherapy has not yet proved to be of major clinical value, suggestions of improving efficacy have been noted over the past decade. A small but real fraction of complete responses has been obtained with combination chemotherapy in patients with favorable prognostic characteristics. A few studies of adjuvant chemotherapy, given after surgery or in conjunction with definitive irradiation, have demonstrated improved disease-free or overall survival periods. Future approaches suggested by laboratory observations of tumor cell biology, such as identification of patients more likely to respond to chemotherapy and early detection of patients at high risk, to develop lung cancer, may eventually prove useful.
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PMID:Future directions in the treatment of non-small cell lung cancer. 216 48

DNA from tumor samples of 54 patients with operable non-small cell lung cancer (NSCLC) was analyzed to determine whether proto-oncogene alterations could be correlated with the clinical behavior of lung cancer. Among seven proto-oncogenes tested, changes in the copy number of Ha-ras, c-myc and c-raf-1 were found in only seven tumors. Most of them were epidermoid carcinomas without lymph node involvement (N0). In spite of a localized disease with complete surgical resection, six of these patients relapsed within a mean disease-free interval (DFI) of only 6.5 months. There is a significant correlation between DNA alterations at proto-oncogene loci and clinical relapse within 12 months of surgical resection (P less than 0.025).
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PMID:DNA alterations at proto-oncogene loci and their clinical significance in operable non-small cell lung cancer. 216 42

Synaptophysin is a Mr 38,000 integral membrane glycoprotein expressed by a variety of normal and neoplastic neuroendocrine cells. We studied synaptophysin as an immunocytochemical marker for neuroendocrine differentiation in lung cancer and compared it to the immunocytochemical expression of chromogranin A, a marker for dense core (endocrine) granules, and the biochemical activity of L-dopa decarboxylase (DDC), the key amine-handling enzyme. Of the 250 cell lines available to us, we selected examples representative of the following cell types: bronchial carcinoids (n = 4), small cell lung cancer (SCLC) (n = 7), extrapulmonary small cell carcinomas (n = 4), and non-small cell lung cancers (n = 18) whose neuroendocrine status had been previously determined on the basis of electron microscopy and DDC activity. We demonstrated (a) there was a higher incidence of synaptophysin than chromogranin A immunoreactivity in carcinoid (100 versus 75%), classic SCLC (70 versus 50%), and variant SCLC (57 versus 29%) cell lines; (b) 3 of the 4 (75%) extrapulmonary small cell lung cancer cell lines expressed synaptophysin and chromogranin A; (c) 5 of the 7 (71%) non-small cell lung cancer cell lines previously shown to express multiple neuroendocrine markers were positive for synaptophysin, chromogranin A, and DDC activity; (d) none of the other 11 non-small cell lung cancer cell lines expressed synaptophysin or chromogranin A; and (e) formalin fixation and paraffin embedding reduced synaptophysin immunoreactivity in 11 of 14 (79%) of the cell lines, as compared to freshly prepared specimens fixed in 95% ethanol. Western blot analysis using the synaptophysin antibody (SY38) demonstrated immunoreactive proteins ranging from Mr 43,000 to 45,000 in five representative cell lines. The concordance of expression of all three neuroendocrine markers was statistically significant when values for all cell lines were totalled. Synaptophysin was a more commonly expressed marker for variant SCLC cell lines, which rarely showed DDC activity. We conclude that synaptophysin may be a more sensitive and specific marker for neuroendocrine differentiation, when compared to chromogranin A and DDC in lung cancer cell lines which express only part of the neuroendocrine program.
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PMID:A comparison of synaptophysin, chromogranin, and L-dopa decarboxylase as markers for neuroendocrine differentiation in lung cancer cell lines. 216 88

The nuclear diameters (NDs) of randomly selected malignant cells from 35 cases of small-cell lung cancer (SCLC; 4,370 nuclei) and 31 cases of non-SCLC (NSCLC; 1,280 nuclei) were measured on the pretreatment tissue sections by ocular micrometry. The mean ND (+/- standard deviation) of malignant cells for SCLC patients was 8.1 +/- 1.5 microns; these cases included 23 oat-cell carcinomas and 12 intermediate-cell carcinomas. The ND of malignant cells for NSCLC patients was 12.8 +/- 2.2 microns; these cases included 17 squamous-cell carcinomas, 12 adenocarcinomas and 2 large-cell carcinomas. The differences of ND between SCLC and NSCLC and between intermediate-cell cancer and NSCLC were highly significant (P = 0.001). However, the malignant cells of 36 (54.5%) of the 66 lung cancer patients had NDs that overlapped in the range of 8 microns to 13 microns. For the 12 intermediate-cell patients, the NDs of the malignant cells overlapped with those of 8 (66.7%) of the 12 adenocarcinomas and 10 (58.8%) of the 17 squamous carcinomas. In contrast, the NDs of only 5 (21.7%) of the oat-cell patients overlapped with those of 5 (41.7%) of the 12 intermediate-cell cases and showed no overlap with NSCLC cases. Since there is overlapping of the nuclear diameters of malignant cells between SCLC and NSCLC patients, nuclear parameters other than the diameter are necessary to differentiate these two major histologic types of lung cancers.
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PMID:Overlap of nuclear diameters in lung cancer cells. 216 53

Recent studies have shown that lung cancer patients frequently suffer inactivation of antioncogenes such as Rb gene (13q14) and p53 gene (17p13). In a study of 48 cases of non-small cell lung cancer (28 squamous-cell carcinomas, 11 adenocarcinomas, 4 large-cell carcinomas, and 5 other types) using restriction fragment length polymorphism analysis, we found DNA sequence deletions from chromosomes 1p32-36, 3p21, 11p15.5, and 11q13. The frequencies of allele loss on chromosome 1p, 3p, 11p and 11q are 31, 57, 20 and 49% of informative cases in this patient group, respectively. Of them, 19 tumors show one allele loss and 10 patients suffer two or more allele losses from different chromosomes.
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PMID:[Allelic losses on chromosomes 1p, 3p, 11p, 11q in non small cell lung cancers]. 216 74

To determine the role of lung cancer tumor imaging with monoclonal antibodies directed against high molecular weight human milk fat globule antigens, we administered i.v. 111In-KC-4G3 to 24 patients with advanced non-small cell lung cancer. One mg of 111In-KC-4G3 was mixed with 0, 9, 49, 99, or 499 mg of unlabeled KC-4G3 and infused i.v. over 1 to 5 h. The mean 111In-KC-4G3 radiochemical purity was greater than 97% and the resultant immunoreactivity averaged 62%. Successful imaging of cancer sites was accomplished in 92% of 24 patients, and 57% of 91 total lesions were visualized. Successful localization of tumor sites related to size (P less than 0.001), with 81% of lesions greater than 3.0 cm in diameter, 50% of lesions 1.5 to 3 cm, and 6% of lesions less than 1.5 cm successfully imaging, and to location (P less than 0.05), with 69% of pulmonary lesions, 80% of soft tissue lesions, and only 32% of bone metastases being visualized. Nonspecific reticulo-endothelial uptake of radioactivity was a major problem. Approximately 35% of 111In was chelated to serum transferrin by 24 and 48 h after infusion. The mean t 1/2 beta for plasma radioisotope and immunoreactive KC-4G3 was 29 and 27 h, respectively. There was no correlation between total infused antibody dose and imaging success or between total dose and effect on 111In and KC-4G3 kinetics. Circulating free KC-4 antigen was measurable in all but one patient before study. Tumor biopsy following infusion could demonstrate antibody presence but not saturable antigen binding. We conclude that (a) 111In-KC-4G3 demonstrates successful tumor localization in non-small cell lung cancers bearing generally high expression of its antigen and (b) further investigations to diminish nonspecific radioactivity for imaging and utilization of high dose radiolabeled antibody for therapeutic intent are warranted.
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PMID:Imaging of non-small cell lung cancers with a monoclonal antibody, KC-4G3, which recognizes a human milk fat globule antigen. 217 15

Studies have suggested that recombinant tumor necrosis factor-alpha (TNF-alpha) may potentiate the killing of murine tumor cells by drugs targeted at DNA topoisomerase II. We have examined the combined cytotoxic effects of the topoisomerase-targeted drug etoposide and TNF in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cell lines using clonogenic assays and a novel flow cytometry technique relying on differential uptake of fluorescein diacetate (FDA) and propidium iodide (PI) by viable and nonviable cells. Good correlation of IC50 determinations for etoposide were noted between clonogenic assays and the FDA/PI technique for both classic and variant SCLC cell lines. The effects of etoposide on the classic SCLC line H209 were potentiated by TNF with a decrease in the IC50 from 3.3 microM to 1.0 microM as determined by FDA/PI. Tumor necrosis factor alone had little effect on the growth or cloning efficiency of H209 cells. Tumor necrosis factor alone stimulated the growth and cloning of variant SCLC line N417, but the cytotoxicity of etoposide was not potentiated by TNF in N417 cells. Tumor necrosis factor alone inhibited the growth and cloning of the NSCLC line H125 but exerted a marked protective effect against higher concentrations of etoposide. It appears that the interaction of TNF with etoposide varies between cell lines and between subclasses of human lung cancer.
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PMID:Interaction of recombinant human tumor necrosis factor and etoposide in human lung cancer cell lines. 217 61


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