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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vivo animal studies support the concept that monocytes and macrophages are important in the immune surveillance of oncogenesis and that in vitro activated murine macrophages are cytocidal for tumour cells. In this study, the tumour cell cytotoxic activity of human peripheral blood monocytes was examined by measuring the inhibition of 3H-thymidine uptake in the human cancer cell line, established in our laboratory from human squamous cell lung cancer. The monocytes from 8 of the 31 lung cancer patients (26%) showed a percentage growth inhibition of less than 69.8%, which exceeded the 95% confidence limits of the percentage growth inhibition observed with healthy control monocytes. On the other hand, among the 16 sarcoidosis and the 8 tuberculosis cases no value was below 69.8%. However, there was no significant difference between the growth inhibition and the clinical stages or histological type. When OK-432, a Streptococcal agent, was administered in vivo to patients with lung cancer, an elevation of the growth inhibition was observed in 7 out of 8 patients. It was confirmed that the tumour cell cytostatic activity of the monocyte is suppressed in patients with lung cancer, and these monocyte deficits hinder the inhibition of tumour growth and metastasis.
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PMID:Decreased monocyte-mediated cytostasis of human cancer cell in patients with lung cancer. 385 93

The present status of extracorporeally induced total-body hyperthermia (TBHT) for far-advanced cancer was presented from data collected from Japanese patients given this treatment. TBHT was most effective in lung cancer. In analyzing the anticancer effects of TBHT according to cancer site, the highest efficacy was observed in patients with their main cancer in the lung or liver, irrespective of whether tumorigenesis was primary or secondary. The anticancer effects were more enhanced when TBHT was combined with dosage of cis-DDP. What is important in combined chemotherapy is to determine what agent(s) should be applied and when. The most useful method for examining the thermosensitivity and thermochemosensitivity of agents for drug selection was the human tumor stem cell assay using individual cancer cells. Further, the usefulness of angiotensin II-induced hypertensive chemotherapy during TBHT in augmenting selective drug delivery to tumors was stressed.
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PMID:[Total-body hyperthermia and combined anticancer chemotherapy]. 393 33

In the Seven Countries Study, carried out in Finland, Greece, Italy, Japan, The Netherlands, the United States, and Yugoslavia, among 11,325 "healthy" men aged 40-59 years in 15 years, there were 594 cancer deaths. Among 477 cancer deaths five years after cholesterol measurement, there was a significant excess of lung cancer deaths in the bottom 20% of the cholesterol distributions in the populations. Age, blood pressure, smoking habits, occupation, and relative body weight did not help explain this. A U-shaped relationship between cancer and cholesterol was not seen in any population. Trend analysis with various cutting points indicated increasing risk of lung cancer death at cholesterol levels under 170 mg/dl. The 45 men dead from cancer in the first two years had lower cholesterol levels than their compatriots who died from cancer later but they did not differ in relative weight or fatness. In contrast to relationships for individuals within populations, the highest cancer death rates were in northern Europe, where the general level of cholesterol was also highest. Other characteristics of the populations--age, relative weight, smoking habits, blood pressure, physical activity, and vitamin A and ascorbic acid in the diet--did not help in the attempt to understand the regional differences in cancer mortality. There is no evidence that any of the observed cancer-serum cholesterol relationships among or within the populations involve an effect of serum cholesterol concentration on oncogenesis or cancer mortality but the possibility of such an effect cannot be denied.
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PMID:Serum cholesterol and cancer mortality in the Seven Countries Study. 401 79

When administered prior to or at the time of carcinogen exposure, the phenolic antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are effective inhibitors of carcinogenesis in several target organs. However, chronic, postcarcinogen administration of BHT apparently enhances tumorigenesis in certain animal models for liver and lung cancer. The present study was performed to determine the effects of BHA and BHT on mammary carcinogenesis when antioxidant exposure is limited to defined periods encompassing or following carcinogen availability. At 50 days of age (Time O), virgin female Sprague-Dawley rats (25/group) were given a single intragastric dose of 8 mg of 7,12-dimethylbenz(a) athracene . Basal diet (Wayne Lab Meal) was supplemented with 5000 or 2500 mg of BHA or BHT/kg by the following protocol: 2 weeks before until 1 week after carcinogen administration; 1 week after carcinogen administration until the end of the study; or none. The experiment was terminated 210 days after 7,12-dimethylbenz(a)anthracene administration, and all mammary tumors were confirmed histologically. When administered by the 2 weeks before to 1 week after schedule, both BHA and BHT were effective inhibitors of mammary carcinogenesis. However, the compounds also were active in chemoprevention when administered by the 1 week after to end protocol. These data indicate that the anticarcinogenic activity of antioxidants is not limited to influences on carcinogen metabolism, since both BHA and BHT inhibited mammary tumor induction when their administration was begun following clearance of the carcinogen from the mammary gland. The anticarcinogenic activity of postcarcinogen administration of BHA and BHT in the mammary gland is in contrast to the apparent tumor-enhancing activity of BHT in the liver and lung.
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PMID:Inhibition of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinogenesis by concomitant or postcarcinogen antioxidant exposure. 642 89

The progressive emergence of a close relationship between the formation of blood vessels in the vicinity of tumour cells and the development and spreading of tumours, strongly suggests that angiogenesis might be a prerequisite for tumour development. Angiogenesis starts and develops in response to two sets of extracellular signals: soluble angiogenic factors and extracellular matrix. Different experimental models have been used to study angiogenesis in vivo, but they have numerous limitations. Three-dimensional culture systems reconstitute normal interactions between endothelial cells and the surrounding extracellular matrix. Numerous parameters including angiogenic growth factors and cytokines, cell-to-cell interactions and cell-to-extracellular matrix adhesion influence the growth and differentiation of endothelial cells in vitro as well as in vivo. Angiogenesis plays a major role not only in tumour growth but also in metastasis development. Mechanisms of switching to angiogenic phenotype have been recently described and onset of angiogenic activity is now recognized as another discrete step in tumorigenesis. Tumour cells can induce b-FGF expression and exportation, VEGF and VEGF receptor expression and inactivation of the cancer suppressor gene encoding for a fragment of thrombospondin. A controlled net proteolytic balance produced by tumour cells or endothelial cells is required to favour migration and invasion of endothelial cells and angiogenesis. The hypothesis that assessment of tumour angiogenesis might predict tumour aggressiveness in human cancer has recently gained support from several clinical studies. This has been shown for cutaneous melanoma, breast carcinoma, and non-small-cell lung cancer by quantitation of microvessels in human biopsies using von Willebrand factor or CD3 antigen labelling with specific antibodies. However, more specific and sensitive markers are needed to improve this approach for predicting tumour aggressiveness. Folkman proposed twenty years ago that inhibition of angiogenesis might represent a suitable complementary strategy for the treatment of various forms of cancer. Since then numerous angiostatic compounds have been identified but very few of them fit the required criteria of a potential drug. Fumagillin and particularly its synthetic analogue AGM 1470 might be developed for use in humans in the near future.
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PMID:Tumour angiogenesis. 751 38

Lung cancer is the leading cause of malignancy-related mortality in the U.S. and is predicted to increase over the remainder of this decade. Despite attempts to advance early diagnosis and use combination therapies, the clinical response of this cancer yields an overall 5-year survival rate of less than 15%. Clearly, new strategies for therapy are indicated. Although carcinogenesis is complex, tumor growth beyond 1-2 mm3 is dependent on angiogenesis. One of the potential mechanisms that allows for tumorigenesis is dysregulation of the balance of angiogenic and angiostatic factors that favors net neovascularization within the primary tumor. Numerous studies have investigated the role of a variety of molecules in the regulation of angiogenesis. Recently, interleukin-8 (IL-8), a member of the C-X-C chemokine family, has been found to be an angiogenic factor. In contrast, platelet factor 4 (PF4), another C-X-C chemokine, has been shown to have angiostatic properties. It is interesting that the major structural difference between IL-8 and PF4 is the presence of the NH2-terminal ELR (Glu-Leu-Arg) motif that precedes the first cysteine amino acid residue of IL-8 and is important in ligand/receptor interactions. We hypothesize that angiogenesis associated with tumorigenesis is dependent on members of the C-X-C chemokine family acting as either angiogenic or angiostatic factors. This paradigm predicts that the biological balance in the expression of these C-X-C chemokines dictates whether the neoplasm grows and develops metastatic potential or regresses. In this review we discuss our recent laboratory findings that support this contention and suggest that further elucidation of the biology of C-X-C chemokines in the context of neovascularization of nonsmall cell lung cancer will permit novel targeted therapy aimed specifically at attenuating tumor growth and metastasis.
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PMID:Role of C-X-C chemokines as regulators of angiogenesis in lung cancer. 753 29

Most of the presently available cancer markers are neither specific for malignancy nor allow early diagnosis. However, the recent elucidation of the molecular events occurring during tumorigenesis may provide new markers that are likely to be both specific for cancer and sensitive for early disease. The key molecules undergoing alterations during carcinogenesis are the cellular oncogenes and suppressor genes. Alterations in these genes can be detected in cells shed from malignant and premalignant lesions. Thus, mutant p53 genes have been found in urine from patients with bladder cancer, mutant ras genes in stools from patients with colorectal and pancreatic cancers, and both mutant p53 and ras genes in sputum from patients with lung cancer. These findings show that the genetic alterations in cancer can be detected in fluids or secretions that had contact with the malignant tissue. The preliminary studies, however, had small numbers of both patients and controls and used time-consuming, labor-intensive, and expensive assays. For routine applications, these assays must be simplified, automated, and tested for sensitivity, specificity, and predictive value.
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PMID:Can molecular markers now be used for early diagnosis of malignancy? 758 9

Expression of the RCK gene, which is a target gene on 11q23 of the t(11;14) (q23;q32) translocation in the B-cell lymphoma cell line RC-K8, was studied by Northern and Western blot analyses. The RCK gene product is a member of the D-E-A-D box protein/RNA helicase family. With the use of Northern blot analysis, a 7.5-kb transcript of the RCK gene was shown to be expressed ubiquitously in human and mouse tissues. Polyclonal antibodies against the RCK gene product were raised, and the RCK gene expression pattern was examined in human and mouse tissues. Two different polyclonal anti-rck antibodies detected a specific 54-kilodalton product named rck/p54 in the majority of human and mouse tissues tested by Western blot analysis. However, rck/p54 was shown to be very low in the human brain and was not detectable in lumbar muscle and lung tissues, although RCK mRNA is abundantly present in these tissues. It is of interest that malignant transformed human cells arising from tissues with low or no expression of rck/p54, such as neuroblastoma, glioblastoma, rhabdomyosarcoma, and lung cancer cell lines, produced a moderate amount of rck/p54 protein, suggesting that rck/p54 plays a role in tumorigenesis. In addition, the rck/p54 protein was localized to cytoplasm by immunostaining with the use of laser microscopy and by subcellular fractionation.
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PMID:The rck/p54 candidate proto-oncogene product is a 54-kilodalton D-E-A-D box protein differentially expressed in human and mouse tissues. 761 84

Accumulating evidence suggests that deregulation of the insulin-like growth factor II (IGF2) and H19 genes at 11p15, due to loss of imprinting (LOI), plays a role in the oncogenesis of Wilms' tumors. We previously reported LOI of IGF2 in carcinomas of the lung, a common cancer of adults. We show here that LOI of H19 is also a frequent event in lung cancer development, and correlated with hypomethylation of the promoter region. Furthermore, the present study also revealed that overexpression of H19 is often associated with LOI of H19 in lung cancers retaining both parental alleles, showing a contrast to LOI in Wilms' tumors. Interestingly, in contrast to frequent LOI of the imprinted genes at 11p15, LOI was not observed for the remaining gene known to be imprinted in man, SNRPN at 15q12.
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PMID:Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. 770 Jun 44

Human lung cancer is a complex disease originating in different cell types. In general, tumorigenesis in the lung appears to involve a complex series of molecular, genetic, and histopathologic events, leading to the transformation of normal cells to malignant cells. It is generally believed that it is the accumulation of biologic changes, not necessarily the order in which they occur, that could best describe the transformation of cells. Our knowledge of genetic changes during tumorigenesis in the lung is limited and comes from studies involving animal models and frankly malignant lung tissues. Such studies can be questioned as to their applicability in primary prevention. A vast majority of genetic changes occurring during the preclinical stage are yet to be documented. Study of these preclinical changes would offer a better opportunity for early detection and prevention. Oncogenes and tumor suppressor genes have potential for use as biomarkers in identifying high-risk groups and in early detection. The interaction between nature and nurture is nowhere as evident as in cancers of the lung, which are influenced by environmental exposure, familial inheritance, and metabolic phenotypes. The gene-environment interaction provides several targets for prevention and early detection. Biomarkers, if validated for specificity, sensitivity, and predictive values, could act as markers of exposure, susceptibility, progression, and disease. Validation of these markers, however, would require well-characterized, prospectively collected samples, representing normal, premalignant, malignant, invasive, and metastatic conditions. The NCI has started an initiative for a tissue bank of prostate, bladder, colorectum, head and neck, and lung cancers. Clinical and epidemiological information are also collected for each sample. Study of genetic and molecular changes in collected samples should shed light on the involvement of these changes in the transformation of normal to malignant tissues.
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PMID:Genetics of lung cancer: implications for early detection and prevention. 770 95


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