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)

A computerized tube LAI assay was used to determine the antitumor immune response in lung cancer patients. A standardized assay was established by the use of tumor antigen recovered from the spent medium of lung and colon adenocarcinoma cell lines. Furthermore, modulation of the assay by prostaglandin E2 (PGE2) was used to increase its sensitivity. Of 65 patients with epidermoid lung cancer, 34 (52.3%) had a positive nonadherence index (NAI). The NAI was inversely related to tumor burden, with 31 of 44 (70.6%) patients with lung cancer stages I and II and only 3 of 21 (14%.2%) patients with stage III having positive assays (greater than 30%). Addition of PGE2 to the as say increased the overall sensitivity so that a positive NAI was obtained in 88.6% of patients with lung cancer stages I and II, and 88.6% with stage III, respectively. Of 174 individuals from the control group, positive NAI was found in only 9 and 3.8% of patients with chronic obstructive pulmonary disease and normal controls, respectively. These results support previous observations on the specificity and sensitivity of the LAI assay in the diagnosis and study of human cancer.
 ...
PMID:A computerized tube leukocyte adherence inhibition assay in the diagnosis of human lung cancer. 241 75

The very rapidly expanding knowledge and technologies of molecular biology are reviewed with special reference to problems in the clinical management of lung cancer. Genetic events, tumor-associated antigens, production of murine and human monoclonal antibodies, culture of cell lines, intratumoral phenotypic diversity and squamous-lung-cancer-associated antigens are discussed and related to possible therapeutical approaches. A monoclonal antibody with high specificity for squamous cell lung cancer reacted positively in blood samples and tissue extracts in about 80%. Its use as a marker during follow-up after surgical treatment is demonstrated by examples. It is concluded that there will be limiting factors in the therapeutic use of monoclonal antibodies, such as intratumoral phenotypic diversity. Genetic analysis might be a method for selecting a high risk group of individuals in whom exposure to carcinogenic factors, such as cigarette smoking, would be fatal. Murine monoclonal antibodies can be used in vitro for screening, for histological examination and for prognostic studies. Human monoclonal antibodies should be used for in vivo purposes as well as for the screening of primary tumor and metastases for the therapy. To achieve usable results, the monoclonal antibodies should be raised against the cell membranes that, in particular, are expressed on the stem cells of the neoplastic cell population.
 ...
PMID:On the advent and necessity of molecular biology in the clinical management of lung cancer. 243 92

Clinical trials on efficacy and toxicity of combined use of bleomycetin, 5-fluorouracil and cisplatin in patients with disseminated tumor processes were conducted. Two regimens were applied. Regimen I included intravenous administration of cisplatin in a dose of 100-150 mg/m2 on day 1, intramuscular administration of bleomycetin in a dose of 10 mg on days 2-4 and intravenous jet injection of 5-fluorouracil in a dose of 400 mg/m2 on days 2-4. Regimen II consisted of intramuscular administration of bleomycetin in a dose of 10 mg on days 1-3, intravenous jet injection of 5-fluorouracil in a dose of 400 mg/m2 on the same days and intravenous administration of cisplatin in a dose of 100-150 mg/m2 on day 4. The intervals between the courses amounted to 4 weeks. Complete regression of cervical carcinoma relapsing was observed in 1 patient. In 5 patients i.e. 1 with small-cell lung cancer, 3 with squamous cell lung cancer and 1 with metastases of low-differentiated cancer from an undetected focus to supraclavicular lymph nodes the effect was partial. Long-term stabilization of the disease at the background of the treatment for 6-7 months was stated in 3 patients. On the whole the objective response was in 6 out of 22 patients or in 27 per cent. 7 of them were treated with cisplatin in a dose of 150 mg/m2. The regimens of the combined use of 5-fluorouracil, bleomycetin and cisplatin were low toxic. The therapeutic effect showed that the combination was of practical value.
 ...
PMID:[Elaboration of the combination of antitumor preparations bleomycetin + 5-fluorouracil + cisplatin]. 246 47

A total of 45 patients with locally advanced and/or metastatic non-small-cell lung cancer (NSCLC) were treated in a phase II trial with high-dose i.v. infusions of 24 g hydroxyurea over 24 h, with 50 mg/m2 i.v. cisplatin 8 h after the start of hydroxyurea infusion. Hydroxyurea, a cell-cycle-specific inhibitor of ribonucleotide reductase, inhibits DNA repair by depleting nucleotide pools. We gave hydroxyurea to achieve steady-state levels of greater than or equal to 1 mM and to potentiate therapy by inhibiting repair of DNA damage produced by cisplatin. Among 21 patients with squamous cell lung cancer, there were 1 complete response (CR), 2 partial responses (PR) and 3 minor responses (MR). Of 13 patients with adenocarcinoma of the lung, 2 had MRs; of 11 patients with large-cell anaplastic lung cancer, none responded. The dominant toxicity was nausea and vomiting, which was manageable and mainly related to cisplatin. The response rate in squamous cell lung cancer was similar to responses obtained with cisplatin alone. The relative ineffectiveness of high-dose 24-h infusions of hydroxyurea in inhibiting repair of DNA damage produced by cisplatin may be due to the low growth fraction of human NSCLC. The high-dose hydroxyurea approach may be more applicable in tumours with a high growth fraction.
 ...
PMID:Cisplatin with high-dose infusions of hydroxyurea to inhibit DNA repair. A phase II study in non-small-cell lung cancer. 253 51

The purpose of this ongoing study is to determine whether thoracic radiotherapy for lung cancer produces an early increase in serum copper (Cu) concentration, an increase which might predict clinical outcome. Copper and iron concentrations were measured in serum obtained from nonsmall cell lung cancer patients at 0, 1, 2, 4, and 6 weeks after the start of radiotherapy. Control groups included patients irradiated for breast cancer (low dose of radiation to the lung), for endometrial, cervical or prostatic cancer (no dose to lung), and patients with congestive heart failure, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and cutaneous burns with or without smoke inhalation (no irradiation). Serum Cu concentration increased at least 10 micrograms/dl from the pretreatment level in approximately 75% of the adenocarcinoma and squamous cell lung cancer patients, but in only 1 of 4 undifferentiated lung cancer cases. In virtually all of these responders, serum Cu increased to a maximum at 2 weeks after the start of therapy, then plateaued or decreased slightly despite continuing irradiation. Within the subset of squamous cell lung cancers, there was a direct correlation between the degree of histologic differentiation and both baseline serum Cu concentration and the probability of an early increase therein. In contrast, only 33% of breast cancer patients and 15% of endometrial, cervical and prostate cancer patients exhibited an increase in serum Cu concentration at 2 weeks after the start of radiotherapy. Serum Cu concentration was within normal limits in virtually all patients with congestive heart failure, pulmonary hypertension, and COPD. Burn patients exhibited a significant reduction in serum Cu, although concomitant smoke inhalation increased serum Cu back to low-normal levels. Serum iron concentration did not change significantly in any category of patients. These data suggest that thoracic radiotherapy for well differentiated non-small cell lung cancer is accompanied by an early increase in serum Cu concentration. This increase is partly but not wholly related to lung dose in particular rather than tissue dose in general, and specifically reflects radiation-induced lung injury rather than pneumopathy in general. In lung cancer patients, the change in serum Cu concentration during the first 2 weeks of radiotherapy exhibits a sufficiently broad range (+60 to -13 micrograms/dl) to permit testing this parameter as a predictor of tumor response and pulmonary complications.
 ...
PMID:Serum copper concentration as an index of clinical lung injury. 262 91

Previous studies have shown that ploidy is an important prognostic determinant in lung cancer, but in those studies followup was restricted to three years, while patients with Stage 1, 2 and 3 disease and with different histological subtypes were included. Theoretically, these factors could have influenced the findings, especially since aneuploidy strongly correlated with the stage of disease. Because of this, tumor ploidy was studied in surgically resected stage 1 (T1/2, N0M0) squamous cell lung cancer patients with a minimal followup of 6 years. All patients were accurately staged by mediastinal lymph node mapping. Fifty-two from a group of 1539 patients with lung cancer diagnosed between 1980 and 1986 inclusive, fulfilled these criteria. Of these tumors, 23 (44%) were diploid with a 6-year survival of 53% and 29 (56%) were aneuploid with a 6-year survival of 48%. Although diploidy tended to be associated with local relapse of the tumor and aneuploidy with distant metastases, the difference was not significant and neither showed a survival advantage. However, within the aneuploid tumors, there was a significant correlation between the percentage of aneuploid cells and survival, defined as event-free or time to death. Seventeen patients with a percentage of more than 10 had a worse outcome (12 died, 6 years survival 35%), than to the other 12 patients with less than 10% aneuploid cells (2 died, 6-year survival 78%) (Mantel-Cox = 6.04, P = 0.01). This implies that in patients with accurately staged and histologically proven Stage 1 squamous cell lung cancer and long-term follow up, DNA content classified as diploid and aneuploid is not a prognostic factor for survival, but the percentage of aneuploid tumor cells is correlated with the prognosis.
 ...
PMID:The percentage of aneuploid cells is significantly correlated with survival in accurately staged patients with stage 1 resected squamous cell lung cancer and long-term follow up. 291 Apr 13

The bronchial epithelium in stepwise transverse sections was examined histologically in 66 male autopsy cases, composed of the groups of 19 mustard gas (MG) ex-workers with lung cancer, 17 MG ex-workers with non-lung cancer, 10 non-MG lung cancer cases, and 20 non-MG non-lung cancer cases. Foci of moderate or severe atypical cellular lesion or dysplasia, or of carcinoma in situ (CIS) in total slides of each group, were counted as 146 in 3,485, 72 in 2,226, 70 in 3,797, and 18 in 4,611, respectively. The relative frequency of moderate or severe dysplasia and CIS in MG exposed non-lung cancer cases resembled that found in lung cancer cases of both MG and non-MG exposed. Seven CIS lesions were detected from among all MG-exposed cases and one CIS was found in a non-MG lung cancer case. Six out of eight CIS examples were adjoined by dysplasia. A multi-variate analysis revealed a significant correlation between the incidence of atypical lesions and MG exposure, though the incidence of atypical lesions was also influenced significantly by age, smoking, and chronic bronchitis. The incidence of atypical lesions was significantly higher in cases of squamous cell lung cancer than those of other histological types, particularly small cell cancer.
 ...
PMID:Early cancer and related lesions in the bronchial epithelium in former workers of mustard gas factory. 301 12

Molecular and cell biologic studies of a large number of lung cancer cell lines of all histologic types have revealed several mechanisms active in the pathogenesis of these cells. Small cell lung cancer (also called "oat cell" lung cancer) has a deletion involving chromosome region 3p(14-23) that is confirmed by DNA restriction fragment length polymorphisms analysis (studies done in collaboration with Dr. Susan Naylor). Several lung cancers of both small cell and non-small cell type (including adeno- and squamous cell lung cancer) express the proto-oncogenes c-, N-, or L-myc, and in some cases more than one of these family members. N-myc appears restricted in its expression to the small cell lung cancer type while c-myc and L-myc can be expressed in both small cell and non-small cell lung cancers. Many lung cancers of all histologic types also express large amounts of p53, which are not correlated with the amount or type of myc gene product expressed. In small cell lung cancer, high levels of myc gene expression are usually associated with gene amplification, and not uncommonly there is rearrangement of some of the amplified copies. In non-small cell lung cancer, expression without amplification or rearrangement of myc genes is seen. In contrast, high level expression of p53 is not associated with gene amplification in any lung cancer type. In addition, to these proto-oncogenes acting at a presumed nuclear locus, there is increased expression of various ras family members and the c-raf-1 proto-oncogene (in collaboration with Dr. Ulf Rapp). Lung cancer cells in tissue culture can grow in medium without serum and few or no other growth factors added. Thus, it appears that lung cancer cells can produce their own growth factors which can act in an "autocrine" fashion. The best characterized example of this is gastrin releasing peptide (GRP, also called bombesin) produced by small cell lung cancer. In at least some small cell lung cancers, interference with GRP action by specific monoclonal antibodies results in inhibition of tumor cell growth in culture and in nude mouse xenografts. Thus, constitutively expressed GRP gene may function as a cellular oncogene under certain circumstances in small cell lung cancer. Based on these observations we are proposing to test monoclonal anti-GRP antibodies in patients.
 ...
PMID:Chromosomal deletion, gene amplification, alternative processing, and autocrine growth factor production in the pathogenesis of human lung cancer. 333 4

T-cell subsets in the peripheral blood of 63 primary lung cancer patients (23 with adenocarcinoma, 23 with squamous cell carcinoma and 17 with small cell carcinoma) and 24 normal healthy controls were determined by indirect immunofluorescence, using the monoclonal antibody reagents OKT3, OKT4 and OKT8. Correlations between T-lymphocyte subset values and stages or cell types of disease were sought. Total lymphocytes in the patient group were decreased. However, no significant difference from controls was seen in the percentage of OKT3-positive cells (Pan T-cells) in the cancer patients. The percentage of OKT8-positive cells (cytotoxic/suppressor) was increased in the early stage of disease whereas the percentage of OKT4 positive cells (inducer/helper) remained at the control level throughout all stages. The ratio of OKT4-positive to OKT8-positive T-cells (OKT4/OKT8), reflecting the balance of immunoregulatory T-cells, was, therefore, significantly decreased in patients with stage I-II lung cancer (P less than 0.05), especially in squamous cell lung cancer (P less than 0.05), whereas in stages III or IV, this T4/T8 ratio returned to the control level. In small cell carcinoma, the T4/T8 ratio was significantly decreased in stage III (P less than 0.01) and returned to the control level in stage IV.
 ...
PMID:T-lymphocyte subsets in primary lung cancer. 349 39

A canine model of squamous cell lung cancer has been developed through studies with 110 dogs exposed by 11 focal endobronchial regimens to chemical carcinogens: benzo(a)pyrene, nitrosomethylurea, methylcholanthrene, and dimethylbenzanthracene. A combination of nitrosomethylurea and benzo(a)pyrene caused the first invasive cancer after 5.5 years. Toxic side-effects resulted from either nitrosomethylurea or high-dose dimethylbenzanthracene given by bronchial submucosal injection and from adjuvant immunosuppression with azathioprine and corticosteroids. Four regimens in 58 dogs caused 31 cancers, including five T1-2 N0 M0 cancers, 17 metastasizing carcinomas, and nine carcinomas of lesser stages. The following regimens caused cancers: sequential benzo(a)pyrene, nitrosomethylurea, and yttrium 91; benzo(a)pyrene and topical nitrosomethylurea; low-dose dimethylbenzanthracene; high-dose methylcholanthrene. The most suitable regimen to date has been 30 mg of methylcholanthrene given by submucosal injection every 2 to 3 weeks; this produced cancers at preselected sites within 2 years of first exposure in eight of 10 dogs. The neoplastic continuum has followed a predictable, reproducible sequence that regularly began with epithelial hyperplasia. Squamous metaplasia occurred in 6 to 18 weeks; it was followed by progressive squamous atypia. The interval until invasive cancer developed varied with the regimen employed; it was about 20 months with methylcholanthrene. Serial cytologic specimens, studied by image analysis, revealed progressive increase in mean total cellular deoxyribonucleic acid content from diploid in normal cells to greater than tetraploid in cancer cells (p less than 0.01). We have recently been successful with serial passage of four canine lung cancers from four to twelve transplant generations in nude mice. There is now a predictable large animal model of squamous cell lung carcinoma at preselected site(s) that closely resembles human lung cancer. The preneoplastic period is short enough to be fiscally defensible, but long enough to permit study of the biologic changes during endobronchial carcinogenesis.
 ...
PMID:Endobronchial carcinogenesis in dogs. 377 44


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