Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of combined high-dose etoposide with standard dose cisplatin was evaluated in patients who had refractory lung cancer after standard chemotherapy. Each patient was given etoposide at 500 mg/m2/day on day 1 to 3 continuously (total dose 1,500 mg/m2) and cisplatin at 80 mg/m2 on day 1. Fifteen patients (7 adenocarcinoma, 5 small cell lung cancer, 2 squamous cell lung cancer and 1 sarcoma, which latter was difficult to distinguish from giant cell carcinoma) were entered in this study. The overall response was 41.7% (5 of 12); five partial response, 6 no change, and 1 progressive disease. Three treatment-related deaths were observed; one resulted from sepsis and two from respiratory failure because of tumor progression. All of the patients developed severe myelosuppression; the mean nadir white blood cell count was 400, and the mean nadir platelet count was 24,000 in 28 evaluable courses. The range of maximum concentration of etoposide determined by HPLC was from 17.4 to 39.1 micrograms/ml. These results suggest that high-dose etoposide combined with a standard dose of cisplatin is effective against refractory lung cancer.
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PMID:[Pilot phase II trial of high-dose etoposide combined with cisplatin in the treatment of refractory lung cancer]. 131 97

CGP 6809 [ethyl-6-deoxy-3,5-di-O-methyl-6-(3-methyl-3-nitrosoureido)-alpha-D- glucofuranoside] is a new methylnitrosoureido-sugar derivative that has been shown to be active against a broad spectrum of transplantable tumours in mice and rats. We investigated the anti-tumour effect of CGP 6809 in ten selected, human tumour xenograft lines growing s.c. in nude mice. The p.o. administration of 125 mg/kg per day for 10-15 days was less toxic (lethality 12% in tumour-bearing nude mice) than the i.p. injection of 62.5 mg/kg per day (lethality 22%). The anti-tumour effect was similar for both application routes; two large bowel cancers responded to treatment with CGP 6809, rectal cancer CXF 158 showed a remission, and the rapidly growing, undifferentiated colonic cancer CXF 280 exhibited a transient no-change. Furthermore, remissions were observed in the epidermoid lung cancer LXF 322 and in thyroid cancer 117. Tumour progression was found in another epidermoid lung cancer and in three stomach cancers, one melanoma, and one soft tissue sarcoma. CGP 6809 is a promising new agent for clinical trials, especially for large bowel and epidermoid lung cancer.
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PMID:CGP 6809--a new nitrosoureido-sugar derivative with activity in human tumor xenografts. 271 55

Forty-one patients with advanced squamous cell lung cancer and no prior chemotherapy were entered in a prospectively randomized trial comparing dianhydrogalactitol plus Adriamycin (DA) versus DA plus cis-dichlorodiammineplatinum(II) (DAP). The DAP regimen was superior to the DA regimen in regression rate (53% versus 27%), median regression duration (255 versus 122 days), median time to tumor progression (approximately 175 versus 58 days), and median survival time (185 versus 126 days). Patients who were greater than 60 years old responded particularly well to the DAP regimen and accounted for most of the survival advantage. Nausea, vomiting, and myelosuppression were more frequent and severe with the DAP regimen. This study seems to indicate a role of cis-dichlorodiammineplatinum(II) in patients with advanced squamous cell lung cancer. The particular advantage noted for older patients needs further evaluation.
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PMID:A role of cis-dichlorodiammineplatinum(II) in squamous cell lung cancer. 699 Nov 7

Restriction fragment length polymorphism in the human c-Ha-ras-1 locus, associated with a minisatellite sequence, was examined in 45 multiple primary cancer (MPC) patients, 56 patients with squamous cell lung cancer (SCLC), 21 patients with lung adenocarcinoma (LAC), and 53 individuals having no oncopathology. Southern analysis of cellular DNA revealed the presence of 4 common alleles (with collective allele frequency close to 94% in the control group) and a set of rare alleles. Allele a3, (2.1 kb in size under MspI/HpaII digestion) was shown to be more frequent in the MPC than in the control group. The same tendency was observed in the patients with highly differentiated cell lung cancer. An increased frequency of the a4 allele (2.5 kb under MspI/HpaII digestion) was observed in the patients with adenocarcinomas as well as in the patients with metastases and low levels of tumor tissue differentiation. The elevated frequencies of a3 in the MPC group and of a4 in the LAC patients did not correlate with increased risk of the cancers mentioned above but was associated with type of tumor progression. Previously, it was reported that the mini-satellite sequence within the c-Ha-ras-1 locus possesses enhancer activity. Our data indirectly confirm the hypothesis that the efficiency of minisatellite modulator activity is associated with fragment size.
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PMID:[Restriction polymorphism of the proto-oncogene c-Ha-ras-1 in patients with multiple primary malignant neoplasms and non-small-cell lung cancer]. 916 92

Fibronectin (FN) is a glycoprotein component of connective tissue. It is involved in cancer progression. FN plays a role in non-neoplasmatic lung pathology in which fibronectin gene polymorphisms (RFLPs) have been studied. The aim of our work was to evaluate the frequency of two of fibronectin RFLPs: genotypes AB, AA, BB (HaeIII) and CD, CC, DD (MspI) in patients with lung cancer. The studied group consisted of 63 patients with squamous cell lung cancer and 53 controls without any malignant or proliferative disease. There were no statistically significant differences in the distribution of studied genotypes between lung cancer patients and controls.
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PMID:Fibronectin gene polymorphism in patients with lung cancer. 1160 51

Lung cancer is highly heterogenous and is composed of various subtypes that are in diverse differential stages. The newly identified integrin-interacting proteins Kindlin-1 and Kindlin-2 are the activators of transmembrane receptor integrins that play important roles in cancer progression. In this report we present the expression profiles of Kindlin-1 and Kindlin-2 in lung cancers using patient specimens and established their correlation with lung cancer progression. We found that Kindlin-1 was expressed in epithelia-derived non-small-cell lung cancer, especially in squamous cell lung cancer but expressed at low levels in poorly differentiated large cell lung cancer. However, Kindlin-2 was highly expressed in large cell lung cancer. Both Kindlin-1 and Kindlin-2 were found not expressed or expressed at very low levels in neuroendocrine-derived small cell lung cancer. Importantly, the Kindlin-1 expression level was positively correlated with the differentiation of squamous cell lung cancer. Surprisingly, we found that the very homologous Kindlin family proteins, Kindlin-1 and Kindlin-2, displayed counteracting functional roles in lung cancer cells. Ectopic expression of Kindlin-1 in non-small-cell lung cancer cells inhibited in vitro cell migration and in vivo tumor growth, while Kindlin-2 promoted these functions. Mechanistically, Kindlin-1 prohibited epithelail to mesenchymal transition in non-small-cell lung cancer cells, while Kindlin-2 enhanced epithelail to mesenchymal transition in these cells. Taken together, we demonstrated that Kindlin-1 and Kindlin-2 differentially regulate lung cancer cell progression. Further, the expression levels of Kindlin-1 might be potentially used as a marker for lung cancer differentiation and targeting Kindlin-2 might block the invasive growth of large cell lung cancer.
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PMID:Opposite role of Kindlin-1 and Kindlin-2 in lung cancers. 2320 5