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

The outcome of thirty-seven patients with a post-resection locoregional recurrence of non-small cell lung cancer treated with radiation therapy alone between 1979 and 1989 was compared to that of 759 patients with unresected non-small cell lung cancer also treated with standard radiation during the same period. Each patient's locoregional recurrence was staged using the current American Joint Committee on Cancer staging system. Comparison of pretreatment characteristics between the two groups, including age, sex, extent of weight loss, performance status, stage, and histologic subtype revealed fewer patients with greater than 5% weight loss (35 vs. 47%, p = 0.04) and more cases with squamous histology (54 vs. 28%, p = 0.01) among the patients with locoregional recurrences than those with newly diagnosed lesions. Over 80% of both groups had clinical stage III lesions. The median radiation doses were 56 and 59 Gy for recurrent and newly diagnosed cases (p = NS). For the patients with locoregional recurrences, the median time from resection to recurrence was 13 months (range: 3-118 months), and the recurrences were predominantly nodal in 25 cases, chest wall/pleural in four and at the bronchial stump in eight. When measured from the date of documented recurrence, the median survival time and 2-year actuarial survival rate of the patients with recurrent lesions were 12 months and 22%, as compared to 12 months and 26% for the newly diagnosed patients (p = NS). Freedom from documented locoregional tumor progression at 2 years was 30% for both groups. Patients with bronchial stump lesions had superior survival to those with nodal or chest wall recurrences, with a median survival time of 36 versus 9 months. A therapeutic approach to selected patients with post-resection locoregional recurrence of non-small cell lung cancer equally aggressive to that for newly diagnosed lung cancer patients is justified by these results, especially for patients with bronchial stump recurrences.
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PMID:Should patients with post-resection locoregional recurrence of lung cancer receive aggressive therapy? 132 98

Small cell lung cancer (SCLC) tumor progression can involve partial or complete conversion to a more treatment-resistant non-small cell (NSCLC) phenotype. In a cell culture model of this phenomenon, we have previously demonstrated that insertion of the viral Harvey ras gene (v-Ha-ras) into SCLC cell lines with amplification and overexpression of the c-myc gene induced many NSCLC phenotypic features. We now report that the v-Ha-ras gene can also induce morphologic, biochemical, and growth characteristics consistent with the NSCLC phenotype in an N-myc amplified SCLC cell line, NCI-H249. We show that v-Ha-ras has novel effects on these cells, abrogating an SCLC-specific growth requirement for gastrin-releasing peptide, and inducing mRNA expression of three NSCLC-associated growth factors and receptors, platelet-derived growth factor B chain, transforming growth factor-alpha (TGF-alpha), and epidermal growth factor receptor (EGF-R). TGF-alpha secretion and EGF-R also appear, consistent with the induction of an autocrine loop previously shown to be growth stimulatory for NSCLC in culture. These data suggest that N-myc and v-Ha-ras represent functional classes of genes that may complement each other in bringing about the phenotypic alterations seen during SCLC tumor progression, and suggest that such alterations might include the appearance of growth factors and receptors of potential importance for the growth of the tumor and its surrounding stroma.
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PMID:v-rasH induces non-small cell phenotype, with associated growth factors and receptors, in a small cell lung cancer cell line. 216 28

Forty-seven patients with advanced non-small cell lung cancer (NSCLC) were treated in a multicentre phase II study with pirarubicin (THP), 4'-O-tetrahydropyranyl-doxorubicin using a dosage of 70 mg/m2 every 3 weeks. The median age of the patients was 59 years (range 45-70) and the performance status grade 0-2 (WHO). Thirty-eight patients had stage IV and 9 stage III (UICC). Twenty-six patients had an adenocarcinoma. 19 a squamous cell carcinoma, and 2 a polymorphocellular carcinoma. Six out of 45 evaluable patients achieved a partial remission leading to an overall response rate of 13%. Eighteen patients showed no change (NC), 12 were progressive (PD), 2 patients had early progression (EP), and 7 patients died during the first course with clinical signs of tumor progression (early death). The median survival time was 4.6 months. Leukocytopenia and thrombocytopenia (WHO grade 4) was experienced in 8.5% and 2.1%, nausea and vomiting (grade 2 and 3) by 32% of the patients. There was no cardiotoxicity or other severe side effects. Pirarubicin has only a moderate antineoplastic activity in patients with advanced NSCLC. Observed response rates are similar to those reported for doxorubicin, but the toxic side effects are milder.
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PMID:Pirarubicin in advanced non-small cell lung cancer. A trial of the Phase I/II Study Group of the Association for Medical Oncology of the German Cancer Society. 216 33

From September 1979 to February 1983, 268 patients with unresectable, locally advanced (RTOG Stage III), non-small cell lung cancer were randomized to receive radiation therapy alone (RT) (50 Gy large field and 10 Gy boost), or combined with misonidazole (400 mg/m2 2-4 hr prior to RT daily for 5-6 weeks to a maximum dose of 12 g/m2 or until tumor progression). One hundred twenty-three patients who received irradiation alone and 116 given RT + misonidazole were evaluable for toxicity, time to tumor progression, and survival as of April 1987. The distribution of patient characteristics was similar in both treatment groups; 59% of the patients had a Karnofsky score of 90 or better, 53% had adenocarcinoma or large cell tumors, and 47% had Stage T3 tumors. Complete tumor regression was reported for 33 (27%) patients treated with radiation therapy alone and 24 (21%) who received misonidazole + RT. Median survival was 8 months with RT alone and 7.4 months with misonidazole + RT. Ninety-five percent of the patients have died. Seventy percent of the patients treated with radiation alone and 77% of those treated with misonidazole + RT died of progressive disease. Three patients treated with radiation alone and two with RT + misonidazole died subsequent to radiotherapy-related pneumonitis or pulmonary fibrosis. There was no significant improvement in response rates, local control, or survival for patients who received daily misonidazole along with irradiation compared with patients treated by irradiation alone.
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PMID:Radiation therapy alone or combined with misonidazole in the treatment of locally advanced non-oat cell lung cancer: report of an RTOG prospective randomized trial. 254 97

The progression of preneoplasia into lung cancer can be serially studied in a new canine model that is simpler and more cost effective than previously reported methods of orthotopic endobronchial carcinogenesis. Short segments of bronchus, obtained by pneumonectomy, were placed on the back of 10 dogs in the form of subcutaneous bronchial autografts. These autografts (12 to 14 per dog) became vascularized and lined with normal respiratory epithelium. Four to 12 weeks after autograft implantation, 10% methylcholanthrene in crystalline form was put into 57 autografts and 10% methylcholanthrene in a silicone polymer sustained-release implant was placed into 54 autografts. Ten autografts without carcinogen (one per dog) served as controls. Serial samplings of each autograft during 9 to 97 weeks of carcinogen exposure showed the neoplastic progression from normal bronchial cells to invasive cancer through stages such as atypical squamous metaplasia and carcinoma in situ. To date, cancers have been histologically proved in 60 autografts; 36 were induced by implants and 24 by the crystalline form. Thirty-nine cancers were epidermoid, and the remainder were either adenocarcinomas (n = 3) or poorly differentiated spindle cell cancers (n = 18). The sustained-release implant method resulted in larger autografts with a greater tendency to progress to cancer than the crystalline carcinogens (p greater than 0.025). Therefore, the sustained-release implant is now considered the preferred method. Measurement of nuclear deoxyribonucleic acid by image analysis of nine histologic cancers demonstrated hyperploidy. Deoxyribonucleic acid from the L1 repeated sequence family was demonstrably hypomethylated in spindle cell tumors. Curettement of individual autografts yielded sheets of respiratory epithelium from which 43.5 to 409.5 micrograms of deoxyribonucleic acid was isolated. For the first time, deoxyribonucleic acid from each stage of the neoplastic progression in non-small cell lung cancer is available in adequate quantities for serial biochemical and therapeutic analysis.
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PMID:Non-small cell lung cancer in autogenous subcutaneous bronchial grafts in dogs. 283 61

A radioimmunoassay for neuron specific enolase (NSE), a marker of neuroendocrine differentiation, has been evaluated in small cell lung cancer (SCLC). In untreated patients 25/38 (68%) with localized SCLC had raised blood levels of NSE (greater than 13 ng ml-1), in extensive disease 34/39 (87%) patients had raised NSE levels. In patients with non-small cell lung cancer (NSCLC) the serum levels were raised in 16/94 (17%). In extensive tumours of non-pulmonary origin NSE levels were increased in 24/116 (20%) patients. Longitudinal studies indicated a good correlation between the response to chemotherapy and fall of NSE levels. Tumour progression was accompanied by a rising NSE in 25/29 patients, with doubling times of 7-90 days. In patients with progression with a normal NSE the recurrence was a NSCLC. Cerebral metastases occurring as the only recurrence during clinical complete remission were not accompanied by a rise of NSE. Serum NSE levels provides a valuable monitor for SCLC during and after chemotherapy.
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PMID:Evaluation of a radioimmunoassay for neuron specific enolase in small cell lung cancer. 299 4

In all, 171 patients with histologically verified non-small cell lung carcinoma were treated with ifosfamide 2.0 g/m2 on days 1-5 in combination with (91 patients) etoposide 120 mg/m2 on day 1. Therapeutic regimens were repeated after 4 weeks. Supportive treatment with mesna (20% of the ifosfamide doses at 0, 4, and 8 h) was performed. Cisplatin treatment was supported by mannitol-induced diuretic hydration. The overall response rate of ifosfamide/etoposide was calculated to be 27%, with 1 complete and 24 partial remissions. The median survival time for all patients was 8.5 months, for responders 14 months (P less than 0.05), for patients with no change 9.5 months, and for patients with tumor progression 4 months. With ifosfamide/cisplatin, there were 4 complete and 21 partial remissions (response rate 35%). The median survival time for all patients was 8.3 months, for responders 11.5 months, and for patients with tumor progression 4 months. Age, sex, and histological tumor type had no significant effect on survival. Patients with better performance stage and limited disease lived significantly longer. The main side-effects of the cisplatin combination were vomiting, bone marrow depression, and neuropathy. The etoposide combination was tolerated better. Urotoxicity was not significant, as a consequence of treatment with mesna. The results show that the combination ifosfamide/etoposide or ifosfamide/cisplatin are effective in the treatment of non-small cell lung cancer, being comparable to other combinations of etoposide/cisplatin and vindesine/cisplatin. Because of the better tolerability, the combination ifosfamide/etoposide is superior to cisplatin combinations.
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PMID:Experience with ifosfamide combinations (etoposide or DDP) in non-small cell lung cancer. 302 62

47 tumor samples, 45 of which were obtained at thoracotomy for non-small cell lung cancer were examined for mutational activation of the oncogenes H-ras, K-ras, and N-ras. A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro amplification step was employed. ras gene mutations were present in nine of 35 adenocarcinomas of the lung (all K-ras), in two of two lung metastases of colorectal adenocarcinomas (1 x K-ras, 1 x N-ras) and in one adenocarcinoma sample obtained at autopsy (H-ras). All K-ras and H-ras mutations were in either position 1 or 2 of codon 12, while the N-ras mutation was in position 2 of codon 61. The potential clinical significance of K-ras activation was analyzed using the combined results of this and of our earlier study (S. Rodenhuis et al., New Engl. J. Med., 317: 929-935, 1987). Lung adenocarcinomas with K-ras mutations tended to be smaller and were less likely to have spread to regional lymph nodes at presentation. With a median follow up of 10 months, survival data are still immature. None of six adenocarcinomas of nonsmokers had a K-ras mutation and only one of four who had stopped smoking more than 5 years before. We conclude that mutational K-ras activation is present in about a third of adenocarcinomas of the lung and that the mutational event may be a direct result of one or more carcinogenic ingredients of tobacco smoke. Studies involving larger numbers of patients are required to confirm the association of K-ras activation with smoking and the inverse relation with tumor progression.
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PMID:Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. 304 48

Twenty-three patients with non-small cell lung cancer were treated with a combination of cis-dichlorodiammineplatinum (II) 100 mg/m2 IV on day 1 and VP 16-213 80 mg/m2 IV on days 1-3. Eighteen patients are evaluable for response. Seven partial remissions with a median duration of 3 months (range, 1-13+) have been observed. Three patients exhibit stable disease, and eight patients show tumor progression. Overall survival was 5+ months (range, 1-13+); 7.5 months (range, 3-13+) for responders and 3+ months (range, 1-9+) for non-responders. Hematologic toxicity was acceptable, but poor subjective tolerance (nausea, vomiting, loss of appetite) was the main factor limiting treatment duration.
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PMID:Cis-dichlorodiammineplatinum (II) and VP 16-213 combination chemotherapy for non-small cell lung cancer. 626 80

We conducted a phase I trial in advanced NSCLC to determine the optimal dosage of the new active drug paclitaxel (Taxol), in combination with high-dose ciplastin (CDDP). Taxol was infused over 3 h, followed by CDDP given over 30 min with hyperhydration. Main criteria of selection were the presence of metastatic or locally relapsing pathologically proven NSCLC, stage IIIB or IV and no prior therapy. Out of 17 treated patients, eight objective responses (47%) were documented. Significant but transient neutropenia was observed in steps III and IV. In seven patients, who received more than three courses, treatment was discontinued for severe polyneuropathy in five, cancer progression in one and unrelated disease in one. In conclusion, paclitaxel plus cisplatin, although active, was associated with severe late neurological toxicity prohibiting the administration of multiples courses.
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PMID:Dose-finding study of paclitaxel (Taxol) plus cisplatin in patients with non-small cell lung cancer. European Lung Cancer Working Party. 755 43


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