Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assayed the panel of SCLC MAbs using multi-tissue tumour block (MTTB) slides obtained from Dr. Hector Battifora (City of Hope Hospital, Duarte CA). MTTB slides contain up to 100 different formalin-fixed tumour tissue specimens and can be immunostained with as little as 50 microliters of antibody solution. In this study, the MAbs in the SCLC panel were used to stain slides from a MTTB comprised of eight normal, ten SCLC, ten squamous cell, ten adenocarcinoma and five undifferentiated lung cancer tissues. Many MAbs in the SCLC panel failed to immunostain the lung MTTB whereas many others showed significant immunoreactivity. Of those MAbs that stained SCLC tissue, none was found to be specific; these MAbs also stained NSCLC tissues or normal lung tissues. Some MAbs in the panel immunostained SCLC and NSCLC tissues, but were also reactive to normal lung tissue as well as other normal tissue specimens. A major advantage of immunostaining MTTBs with a panel of MAbs is that we were able to compare the immunoreactivity of the MAbs on a total of 128 different tissues requiring only 100 microliters of antibody solution using only two MTTB slides per MAb. Although this study was preliminary and certain technical problems in assembling the MTTB as well as optimising the immunostaining procedure for handling 98 or more MAbs simultaneously remain, the MTTB technique remains promising.
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PMID:Cross validation of cluster analysis using immunostained multi-tissue tumour block slides. 164 74

A series of bombesin (BN) analogues lacking the C-terminal methionine at the 14 position were evaluated as BN receptor antagonists. [D-Phe6]BN(6-13)amide inhibited specific 125I-GRP binding to lung cancer cell line NCI-H720 with an IC50 value of 12 nM. In contrast, [D-Phe6]BN(6-13)propylamide, butylamide and methylester were more potent with IC50 values of 3, 5 and 5 nM whereas [D-Phe6,Sta13]BN(6-13)amide was less potent with an IC50 value of 180 nM. [D-Phe6]BN(6-13)propylamide antagonized the ability of BN to elevate cytosolic Ca2+, whereas [D-Phe6]BN(6-13)butylamide was a partial agonist. In a small cell lung cancer (SCLC) growth assay, [D-Phe6]BN(6-13)propylamide inhibited colony formation. In summary, BN analogues which lack a C-terminal methionine may function as useful SCLC BN receptor antagonists.
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PMID:[Des-Met14]bombesin analogues function as small cell lung cancer bombesin receptor antagonists. 164 97

The purpose of this report is to review the problems in the evaluation of new drugs in SCLC and phase II testing of analogues in lung cancer. SCLC is one of the most chemotherapy-sensitive solid tumours and patients (pts) who relapse after their first-line treatment are likely to have resistant tumors, precluding the appropriate evaluation of new drugs, especially analogues. However, it is ethically difficult to evaluate new drugs in untreated pts with SCLC. Based on many issues, We recommended that new drugs should be evaluated in "good" pts with extensive-stage SCLC and that the trial design should include early stopping rules as well as a crossover to an active alternative regimen such as etoposide and cisplatin for non-responders. Also, I recommended that the endpoint for a positive phase II study with an analogue depends upon which of the following four ways the analogue's superiority is hope for; (1) superior efficacy in responsive tumors; (2) broader spectrum; (3) cross-over resistance to the parent structure; (4) diminished toxicity.
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PMID:[Phase II study of lung cancer--evaluation of new drug in small cell lung cancer (SCLC) and phase II testing of analogues]. 164 80

Many investigators have studied the benefit of adjuvant chemotherapy (AC) in resected lung cancer. However, its benefit is still controversial, except for small cell lung cancer. In the present study, we discussed problems in the preparation of a phase III trial of AC in resected lung cancer. Since a phase III trial requires generally large sample sizes for a short period, a multicenter approach is frequently necessary. However, there are several problems in the preparation of such trial. Firstly, we found that survival for resected lung cancer was considerably different among institutions. Overall 5-year survival for 279 resected N2 disease collected from 7 major institutions was 23%. The 5-year survival for each institution, however, ranged from 7 to 41%. This difference is probably caused by the fact that surgical indication, an ability in operation and postoperative care are different among institutions. Secondly, the number of patients enrolled in the trial spread widely among cooperative institutions. In a phase III trial of AC for resected stage III A patients, 209 patients were collected from 25 institutions. The number of patients enrolled from individual institutions ranged from 0 to 25. Only 5 institutions were possible to enter more than 10 evaluable patients on the trial. Recently, a phase III trial of neoadjuvant therapy was carried out in stage III A (T1-2N2) patients at 5 major institutions. Patients were treated initially with 2 cycles of chemotherapy (CDDP + VDS + MMC), followed by surgical resection. Of 22 resected patients, 4 who underwent extended pneumonectomy, happened to die postoperatively only in one institution. This also shows an imbalance of surgical results among cooperative institutions. In conclusion, we consider that it is particularly important to select institutions without an imbalance of surgical results in a phase III trial.
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PMID:[Assessment of a phase III trial of adjuvant chemotherapy in resected lung cancer: an imbalance of surgical results among cooperative institutions]. 164 82

The ability of blood lymphocytes of newly diagnosed lung cancer patients to respond to interleukin 2 (IL-2) to become IL-2-activated killer (LAK) cells and its regulation by autologous monocytes were examined. LAK activity was measured by 51Cr release assay. The abilities of lymphocytes among blood mononuclear cells (MNC) of subjects of different ages without malignancies to generate LAK activity against NK-cell resistant Daudi cells and lung adenocarcinoma (PC-9) cells were very similar. The LAK activity of blood MNC of lung cancer patients was also nearly the same as that of blood MNC of control subjects. There was no significant difference in IL-2-inducible LAK activity between MNC of patients with small cell lung cancer (SCLC) and those of patients with non-SCLC. Monocytes and lymphocytes were separated from blood MNC on a one-step Percoll gradient. Monocytes of lung cancer patients were found to augment in vitro induction of LAK activity by IL-2 of autologous blood lymphocytes. In contrast, endotoxin-stimulated monocytes suppressed LAK induction of autologous lymphocytes of cancer patients. These findings suggest that administration of IL-2 and LAK cells induced in vitro may be of benefit in the treatment of lung cancer.
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PMID:Interleukin-2-inducible killer activity and its regulation by blood monocytes from autologous lymphocytes of lung cancer patients. 164 13

Advances in the treatment of limited small-cell lung cancer (L-SCLC) have led to improved short-term outcome. However, it is not clear how well this predicts the ultimate fate of the patients. This may be affected by late relapse of SCLC, the development of second malignancies, and the long-term toxicity of therapy. To address this issue we report follow-up in excess of 5 years on a cohort of 36 patients who had high short-term survival resulting from treatment with chemotherapy combined with cranial and thoracic irradiation. All patients were followed until death or the time of analysis. The initially promising result of 31% survival at 3 years, was reflected in survival from SCLC of 27% at 5 years, and 23% at 9 years. However, when death from all causes was analyzed, survival was only 19% at 5 years and 7% at 9 years. There were 2 survivors disease-free at 7 and 8 years; 7 patients died of other causes without any evidence of SCLC. Among those not dying of SCLC, 4 patients developed second malignancies with a risk of 22% at 3.2 years and 50% at 8 years. Clinical neurotoxicity developed in 3 patients. These data suggest that cure of SCLC is possible in a modest proportion of patients with limited disease, but that the survivors are at significant risk of developing second malignancies which emerge as the most common cause of death during prolonged follow-up. Successful outcome of treatment is further hampered by the occurrence of neurotoxicity. Clinical strategies to prevent these sequelae of therapy are discussed.
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PMID:Limited small-cell lung cancer: do favorable short-term results predict ultimate outcome? 165 May 27

Preliminary results of the 1984 ISC (International Society of Chemotherapy) lung cancer studies I and II as of June 1990 are based on 146 patients with small cell bronchial carcinoma from 23 departments of thoracic surgery. All patients received surgery for cure in cTNM stages I and II followed by randomization for two different types of chemotherapy. For disease-free patients after completion of postoperative chemotherapy, prophylactic cranial irradiation (PCI) was administered. For the two different chemotherapeutic regimens, no statistically significant differences in survival (SVR) could be observed. Each patient was classified by the pTNM system. There were 63 patients with stage I, 44 patients with stage II and 38 patients with stage III disease. Four years after surgery, 63 patients with N0 disease had a SVR of 50%, 51 patients with N1 disease 31%, and 32 patients with N2 disease, 23%. No prolongation of brain-metastasis-free time for 62 patients receiving PCI was shown. It is concluded that initial surgical resection for small cell lung cancer in stages I and II followed by intensive chemotherapy is an appropriate therapeutic approach.
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PMID:Multimodality treatment for small cell bronchial carcinoma. Preliminary results of a prospective, multicenter trial. The ISC-Lung Cancer Study Group. 165 41

We have studied MAbs* for their ability to detect SCLC and differentiate this tumor type from the other lung tumor histotypes in cryostat sections of biopsy specimens taken at bronchoscopy from patients with suspected primary lung tumor disease. MAb F12, specific for the ganglioside fucosyl-GM1, reacted with 58% of the cases with SCLC (n = 19) and with less than 3% of those with non-SCLC (n = 38). MAb 123C3, specifically reactive with NCAM, reacted with 78% of the SCLC cases (n = 23). With this MAb no positive staining was seen in the non-SCLC cases (n = 41). None of the two MAbs reacted with tissue sections without tumor. In combined analysis with MAbs F12 and 123C3, all SCLC cases (n = 15) were positive with either and 47% with both of the MAbs. Our results show that both MAbs F12 and 123C3 are highly specific for SCLC in bronchoscopic biopsy tissue specimens, whereas the sensitivity for this histotype tends to be higher with MAb 123C3 than with F12 (P = 0.14). When used in combination, all SCLC cases could be identified. These MAbs may therefore be valuable as complements to current histopathologic characterization and differentiation of lung cancer.
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PMID:Immunohistochemical detection of two small cell lung carcinoma-associated antigens defined by MAbs F12 and 123C3 in bronchoscopy biopsy tissues. 165 59

The present study examines the relationship between neuroendocrine (NE) differentiation and the clinical behaviour of non-small cell lung cancer (NSCLC). Retrospective (n = 315) and prospective (n = 44) cohorts of non-small cell tumours were obtained from surgically treated cases of lung cancer, comprising 218 squamous cell carcinomas, 65 adenocarcinomas, 51 adenosquamous carcinomas, and 25 large cell undifferentiated carcinomas. Paraffin wax embedded and fresh frozen tissue sections were stained for the NE markers neurone specific enolase, creatine kinase-BB, bombesin, neurotensin, chromogranin A, synaptophysin and UJ-13A. The expression of two or more markers was observed in 30% of cases, and was taken to identify NE-NSCLC. A statistically significant correlation between nodal status and NE differentiation (P = 0.05), and disease stage and NE differentiation (P = 0.04) was observed. However, there was no correlation between NE differentiation and survival. These findings suggest that NE-NSCLC, analogous to SCLC is more highly metastatic than non-NE-NSCLC.
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PMID:Neuroendocrine differentiation and clinical behaviour in non-small cell lung tumours. 165 75

Twelve inoperable lung cancer patients were treated with a combination chemotherapy of cisplatinum (CDDP) and etoposide (VP16), as a continuous infusion for 5 days, every 21 days, and with a daily oral administration of GaCl3. Dosages of CDDP and VP16 were adapted in order to obtain an area under the curve (AUC) of 80,000 micrograms l-1.h for plasma total platinum and of 200 mumol.l-1 h for plasma VP16 during each 120 h infusion. GaCl3 was given at the dosage of 400 mg/24h from the time of diagnosis at least until the evaluation after 3 courses of chemotherapy. An objective response was observed in 5 non small cell (NSCLC) lung cancer patients (group 1) and 3 small cell (SCLC) lung cancer patients (group 2). In the other 4 patients with a NSCLC no partial response was noted (group 3). No significant difference in area under the curve (AUC) was noted between the 3 groups, either for plasma total platinum (group 1 = 89,598 +/- 20,843 micrograms l-1.h; group 2 = 88,081 +/- 15,431 micrograms l-1.h; group 3 = 83,820 +/- 13,455 micrograms l-1.h), or for VP16 (group 1 = 227 +/- 41 mumol.l-1 h; group 2 = 217 +/- 29 mumol.l-1.h and group 3 = 211 +/- 30 mumol.l-1.h). The maximal plasma Ga concentrations were 244 +/- 34 micrograms/l in group 1, 112 +/- 57 micrograms/l in group 3 (p less than 0.005) and 243 +/- 132 micrograms/l in group 2. It was then decided to increase the dose of GaCl3 in the further non-responding patients. In 6 responders, 3 additional courses of this combination chemotherapy could have been given without major toxicity, allowing a much more important decrease in the tumor volume in 4 of them. This schedule of treatment should permit the chemotherapy to continue for longer than 6 courses, in order to improve the survival time.
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PMID:Combination chemotherapy with cisplatin, etoposide and gallium chloride for lung cancer: individual adaptation of doses. 166 Jun 90


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