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)

Retinoids, natural or synthetic derivatives of vitamin A, have been studied as cancer chemopreventive agents and as therapeutic agents in the treatment of solid tumors. Intensive clinical research has focused on the role of retinoids in preventing second primary tumors following head and neck or lung cancer. The frequent occurrence of second primary tumors in these areas provides clinical support for the hypothesis of field carcinogenesis. Based on evidence of its efficacy in reversing oral premalignancy, the synthetic retinoid 13-cis-retinoic acid (13cRA) was studied in a 1-year trial to prevent the incidence of new cancers in patients who had been treated for squamous cell carcinoma (SCC) of the head and neck. Second primary tumors developed in only 4% of 49 patients treated with 13cRA, as compared with 24% of 51 patients treated with placebo (P = .005). These findings have led to two ongoing large-scale trials of 13cRA in North America. One study, performed through the M.D. Anderson Cancer Center and its affiliated Community Clinical Oncology Program and the institutions of the Radiation Therapy Oncology Group (RTOG), will determine whether long-term administration of low-dose 13cRA will prevent second primary tumors following an initial head and neck cancer. Another intergroup study using a similar randomized double-blind design is being performed among patients who have undergone resection of a stage I non-small-cell lung cancer. In Europe, a large chemoprevention study called Euroscan is currently examining the efficacy of another retinoid, retinyl palmitate, in preventing second primary tumors following head and neck or lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Retinoid chemoprevention of second primary tumors. 783 82

The QLQ-C30, a health-related quality of life questionnaire developed for use in patients with cancer, has been previously validated in patients with lung cancer and head and neck cancer. In this study, further validation was carried out for 535 patients, including patients with breast cancer (n = 143) and ovarian cancer (n = 111) for whom there is no previously published validation, as well as patients with lung cancer (n = 160) and a heterogeneous group of other cancers (n = 121). All patients were entered in one of two trials of anti-emetics to prevent chemotherapy-induced emesis. The QLQ-C30 was completed before chemotherapy and on day 8 after chemotherapy. The factor structure in patients with breast and ovarian cancer was similar to that previously described. Interdomain correlations, in the entire group, were strongest for the physical and role function domains and the fatigue, pain and global quality of life domains before and after chemotherapy. In addition, after chemotherapy, social function was also strongly correlated with fatigue and global quality of life. These correlations were not always of equal strength in the breast, ovarian and lung groups, suggesting that there may be differences between these groups. The responsiveness of the QLQ-C30 in the presence of widely metastatic, as compared with locoregional, disease showed changes in the expected directions (i.e., diminished function in physical and social role functions and in global quality of life, with greater fatigue and pain in patients with metastatic disease). Eight days after chemotherapy, decreases were seen in physical, role and social functioning and in global quality of life, and there was greater fatigue, nausea and vomiting compared with before chemotherapy. Patients with breast cancer had better physical, role and social functioning and less fatigue and pain than patients with ovarian cancer. This result is expected, since many of the patients with breast cancer had early stage disease, whereas those with ovarian cancer had advanced stage disease. Mean scores for patients with lung cancer were between the other two groups, in keeping with the mixture of early and advanced stage disease in these patients. There was a strong correlation between ECOG performance status scores and several domains of the QLQ-C30; these were all in the expected directions. The results of this study confirm those in earlier studies on patients with lung cancer, and provide new information on patients with breast and ovarian cancer. In addition, the QLQ-C30 is responsive to the effects of chemotherapy and of metastatic disease.
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PMID:Psychometric properties and responsiveness of the EORTC quality of Life Questionnaire (QLQ-C30) in patients with breast, ovarian and lung cancer. 784 68

Taxol, a diterpene alkaloid isolated from the bark of Taxus brevifolia, has a unique mechanism of action. The drug promotes the formation of microtubule polymers in a cell, by reversibly and specifically binding the beta-subunit of tubulin. Taxol is administered intravenously by a 3-24-hour infusion at 3-week intervals. Myelosuppression, especially neutropenia, appears to be the dose limiting toxicity in solid tumours at 200-250 mg/m2. Furthermore, side effects such as sensory neurotoxicity (with typical numbness, tingling and painful paraesthesiae in the extremities), diarrhoea and alopecia appear frequently. Mucositis appears to be the non-haematological dose limiting side effect at 390 mg/m2 that has been determined in patients with leukaemia. Hypersensitivity reactions, which have been fatal in individual cases, might be schedule dependent. Furthermore, antiallergic prophylaxis must be given, although this precaution might not be considered to be fully protective. Phase I studies performed with combinations of taxol and cisplatin, doxorubicin or cyclophosphamide have indicated the feasibility of these regimens and show promise for future investigations. Addition of granulocyte-colony stimulating factor (G-CSF), aimed at modulating myelosuppressive toxicity, showed in Phase I studies that the taxol dose could be increased to 250 mg/m2, with peripheral neuropathy as the dose limiting toxicity. In Phase II studies, taxol has been shown to be effective, including producing complete tumour remission, in advanced drug refractory ovarian carcinoma (19%-36% response rate), previously treated patients with metastatic breast carcinoma (27%-62% response rate), advanced non-small lung cancer (21%-24% response rate), advanced small cell lung cancer (37% response rate) and advanced head and neck cancer (34% response rate).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical, toxicological and pharmaceutical aspects of the antineoplastic drug taxol: a review. 790 88

Loss of heterozygosity (LOH) affecting chromosome 9p has been shown to occur frequently in head and neck cancer, glioma, mesothelioma, melanoma, lung cancer, and numerous other tumor types. Chromosome 9p is therefore presumed to contain a tumor suppressor gene or genes. Since esophageal cancer shares characteristics with some of the above tumor types, we performed a detailed examination of 60 patients with squamous cell carcinoma or adenocarcinoma of the esophagus for LOH at loci D9S162, IFNA, D9S171, D9S126, D9S104, D9S165, and D9S163. Multiplex polymerase chain reactions were performed with the inclusion of one radiolabeled nucleotide, and products were electrophoresed on denaturing polyacrylamide gels. Thirty-six of the 60 patients (60%) exhibited LOH at one or more loci on chromosome 9p. Eight of 17 patients (47%) with adenocarcinoma manifested LOH, while 28 of 43 (65%) with squamous cell carcinoma showed LOH. LOH was most frequent at loci D9S171 (19 of 23, or 83%) and D9S165 (24 of 32, or 75%). These data support the hypothesis that a tumor suppressor gene or genes located on this portion of chromosome 9p exert(s) an effect on esophageal cancer development.
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PMID:Frequent loss of heterozygosity on chromosome 9 in adenocarcinoma and squamous cell carcinoma of the esophagus. 795 53

Alternating chemoradiotherapy has recently been reported to produce encouraging results in patients with advanced head and neck cancer. We have treated 17 patients with squamous cell carcinoma of the upper esophagus by alternating chemoradiotherapy and by following the patients for 2 to 5 years, or until their death. Chemotherapy (cisplatin and 5-fluorouracil) was delivered during weeks 1, 4, and 7, and radiotherapy (180 to 200 cGy twice each day to 2,000 cGy) during weeks 2, 5, and 8 (total 6,000 cGy). Three patients (18%) died of toxicity (nadir sepsis). All 14 patients who survived the treatment achieved a complete response as shown by endoscopy and biopsy specimens, with restoration of swallowing, and none experienced a local relapse. Three patients died of distant metastases (actuarial incidence 32% at 3 years). The 5-year survival rate was only 16%, however, because 8 other patients with no evidence of the cancer died of a variety of other causes: radiation pneumonitis (1), chronic neutropenia (1), esophageal actinomycosis (1), pneumonia (2), stroke (1), myocardial infarction (1), and small-cell lung cancer (1). Conceivably, some further improvement in the results might occur from cytokines, stem cells, and brachytherapy (by decreasing deaths due to toxicity), but with so many causes of comorbidity it seems unlikely, for the foreseeable future, that the 5-year survival rate could be much improved by better treatment of esophageal cancer.
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PMID:Patterns of failure in carcinoma of the upper esophagus after alternating chemoradiotherapy. 797 65

Quality of life was assessed by self-report questionnaires in 30 patients receiving dose-intensive chemotherapy for either non-small-cell lung cancer (20 patients) or recurrent head and neck cancer (10 patients). Megestrol acetate was given daily to try to improve appetite and prevent the weight loss usually associated with this chemotherapy. Appetite did not change significantly overall during the first 4 weeks of chemotherapy, but it did improve in those patients still receiving chemotherapy at 8 weeks. Changes in global quality of life were significantly correlated with changes in appetite, fatigue, energy level, and physical function. Thus, these parameters may have more relevance to patients' perceptions of quality of life than does weight change, and should be used more frequently as endpoints in studies of supportive care and palliative treatment of patients with cancer.
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PMID:Quality of life, appetite, and weight change in patients receiving dose-intensive chemotherapy. 800 98

Head and neck cancer remains a common cause of mortality and morbidity in the United States and throughout the world. In spite of advances in the management of patients with advanced disease, overall survival in this group remains poor. Furthermore, although cancer mortality is lower in patients with early-stage disease, treatment results in significant morbidity, and these patients also face the risk of developing a second primary tumor. Chemoprevention is an innovative approach to decrease overall cancer morbidity and mortality using substances that are capable of preventing cancer progression. Head and neck cancer is an excellent model for chemoprevention, as its biology is consistent with the two concepts important for the development of chemoprevention strategies: field cancerization and multistep carcinogenesis. Several classes of compounds have been evaluated in chemoprevention trials. The most frequently studied agents, the retinoids, were found frequently to induce remissions in patients with oral leukoplakia. Furthermore, retinoids prevented progression to malignancy in one randomized maintenance study. Other agents, including beta-carotene and vitamin E, have been found also to have activity in the management of oral leukoplakia. However, the clinical role of chemopreventive agents in reducing cancer mortality remains to be defined. Two studies, one in head and neck cancer and one in lung cancer, have shown the ability of retinoids to prevent the development of second primary tumors. Current large randomized trials are defining the effectiveness of these agents in reducing the mortality of aerodigestive tract tumors in individuals at high risk.
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PMID:Biology and chemoprevention of head and neck cancer. 805 3

The most commonly used chemopreventive agents in the prevention of oral leukoplakia, head and neck cancer, and lung cancer are beta-carotene, vitamin A, and other retinoids. One of the few chemopreventive agents not in this group and presently being used in a clinical trial is N-acetyl-l-cysteine (NAC). NAC, an antioxidant, is used in EUROSCAN, a European Organization of Research and Treatment of Cancer (EORTC) chemoprevention study in curatively treated patients with oral, laryngeal, or lung cancer. The rationale for choosing NAC is based on a variety of experimental data showing its ability to exert protective effects, including extracellular inhibition of mutagenic agents from exogenous and endogenous sources, inhibition of genotoxicity of reactive oxygen species, modulation of metabolism coordinated with blocking of reactive metabolites, protection of DNA and nuclear enzymes, and prevention of the formation of carcinogen-DNA adducts. NAC has also demonstrated an effect on mutagen-induced chromosomal sensitivity assays, and on anticarcinogenicity in experimental animal models. In addition, preliminary data from EUROSCAN show good compliance in treated patients and a low frequency of side effects.
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PMID:N-acetyl-l-cysteine. 841 5

Chemoprevention entails using specific agents to suppress carcinogenesis and thereby prevent the development of primary or second primary cancers. Because the concept of chemoprevention in patients with or at risk of lung cancer is new, ongoing clinical trials are based on data from epidemiologic and preclinical research, as well as on results of chemoprevention studies in head and neck cancer. The latter studies have provided a model for such studies in lung cancer, considering the two diseases have a similar etiology and biology of field carcinogenesis. Beta-carotene, natural vitamin A, and the retinoids may be effective chemopreventive agents. However, chronic administration of such agents may be required to prevent the development of cancer. Results of chemoprevention trials in head and neck cancer have demonstrated effective inhibition of the development of second primary tumors with the synthetic retinoid 13-cis-retinoic acid; investigators are hopeful this will be repeated in patients with lung cancer. Results of ongoing phase III trials and continued advances in the epidemiologic and biologic study of lung carcinogenesis should contribute to future research in this area.
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PMID:Chemoprevention strategies in lung carcinogenesis. 841 69

The objective of this study is the evaluation of serum levels of lipid-bound sialic acid (LSA) as a of marker cancer. This is a case-control study, and the levels of LSA were determined with blinded duplicates of cases and controls. Histologic verification of all cancer cases was used to confirm the diagnosis. The study included 135 patients with cancer (breast carcinoma, head and neck squamous cell carcinoma, lung cancer and gastrointestinal cancer) and 95 controls (57 normal subjects and 38 with chronic non-malignant diseases). Marker determination was done by the spectrophotometric procedure of Katopodis with resorcinol. The mean LSA level in the 57 healthy individuals was 15.09 mg/dl(95% C.I., 13.51-16.67), in the entire control group of 95 non-tumoral individuals it was 19.21 mg/dl (17.18-21.24), and in the 135 cancer patients it was 26.64 mg/dl (24.42-28.87). There was a statistically significant difference between patients with chronic non-tumoral diseases and healthy individuals (p < 0.001) and also between cancer patients and healthy individuals (p > 0.001), but not between cancer patients and patients with chronic non-tumoral diseases (p> 0.05). The mean LSA serum values related to tumor site were (mg/dl): breast cancer, 21.49; gastrointestinal tumors, 28.45; head and neck cancer, 28.61 and lung cancer, 32.54. The means according to clinical stage were: complete remission, 18.50 significantly higher than the healthy controls (p< 0.05); local disease, 23.50 (p < 0.01); locoregional disease, (p < 0.05); local disease, 23.50 (p < 0.01); locoregional disease, 27.21 (p < 0.001); metastatic disease, 34.49 (p < 0.001), and relapses, 20.87 (p< 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of lipid-bound sialic acid (LSA) as a tumor marker. 855 Oct 61


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