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Biomedical subjects

N Hara

Publications and source records attributed to N Hara.

At least 73 records · Page 4Linked to original sources
PubMed2000

Alteration of drug chemosensitivity caused by the adenovirus-mediated transfer of the wild-type p53 gene in human lung cancer cells.

The aim of the present study is to identify the optimal anticancer agents for use in combination with gene therapy using wild-type (wt) p53 gene transfer. We used adenoviral vectors expressing human wt p53 (AdCAp53) and investigated the effects of wt p53 gene transfer in combination with 12 anticancer agents on a human pulmonary squamous cell carcinoma cell line, NCI-H157, and a human pulmonary large cell carcinoma cell line, NCI-H1299. Solutions containing anticancer agents at various concentrations were added followed by the addition of recombinant adenovirus solutions; after a 5-day incubation period, the anticancer activity was then evaluated by a 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carbo xanilide assay. Each 50% inhibitory concentration was calculated based on the dose-response curves. The agents showing a high degree of effectiveness on NCI-H157 cells were cisplatin (CDDP), 5-fluorouracil (5-FU), bleomycin, and 7-ethyl-10-hydroxy-camptothecin (SN-38), an active metabolite of irinotecan (CPT-11); conversely, cyclophosphamide and paclitaxel showed a low degree of effectiveness. Based on these data, an isobologram was performed to investigate the interaction between AdCAp53 and some anticancer agents. A supra-additive effect was thus observed for 5-FU and SN-38 on NCI-H157 cells. An additive effect was also observed for CDDP, paclitaxel, bleomycin, and cyclophosphamide on NCI-H157 cells. CDDP, paclitaxel, 5-FU, and SN-38 had an additive effect on NCI-H1299 cells. No drug showed any subadditive or protective effects. These findings suggest that CPT-11 and 5-FU may thus be useful as possible anticancer agents for use in a combination therapy regimen using wt p53 gene transfer. CDDP and CPT-11 had a significant antitumoral effect on H157 cell xenografts of nude mice in vivo. These results indicate that CPT-11 as well as CDDP would be a candidate for the combination of chemotherapy and gene therapy for non-small cell lung cancer.

Adenoviridae↗
PubMed2000

Correlation between diffuse pigmentation and keratinocyte-derived endothelin-1 in systemic sclerosis.

BACKGROUND: The precise mechanism of diffuse pigmentation in systemic sclerosis (SSc) is still unknown. We suspected the participation of endothelin-1 (ET-1), which is produced by keratinocytes, in the hyperpigmentation in SSc. The aims of this study are to demonstrate the hyperproductivity of ET-1 from epidermal cells in SSc by in situ hybridization histochemistry, and to show a correlation between the hyperproductivity of ET-1 in keratinocytes and skin hyperpigmentation. METHODS: In situ hybridization histochemistry was performed on nine SSc specimens (five cases of diffuse scleroderma (dSSc), four cases of acrosclerosis (lSSc)), and compared with four normal control specimens. We counted the grains on 10 x 10 microm(2) of epidermis and microvessels in each histology and examined the degree of skin pigmentation using the skin reflectance factor (Y). RESULTS: In the specimens of the SSc patients, the number of grains on the epidermis was remarkably higher than those of the control specimens (P < 0.01). We found a close correlation between the number of grains and the skin reflectance factor in dSSc patients (P = 0.02). Correlations were not identified between serum ET-1 and skin pigmentation and between serum ET-1 and the frequency of grains on the epidermis. As for grains on microvessels, lSSc patients showed a greater frequency than dSSc patients. CONCLUSIONS: The findings of this study suggest that an increase in the ET-1 productivity of keratinocytes is experienced in SSc patients, especially in dSSc patients. The results suggest a strong correlation between the ET-1 productivity of keratinocytes and skin pigmentation in severe cases of SSc. We conclude from these results that keratinocyte-derived ET-1 plays an important role in the pathogenesis of the hyperpigmentation of the skin in SSc patients.

Adult↗
PubMed2000

A subunit of the mammalian oligosaccharyltransferase, DAD1, interacts with Mcl-1, one of the bcl-2 protein family.

DAD1 is a mammalian homologue of Saccharomyces cerevisiae Ost2p, a subunit of the oligosaccharyltransferase complex. Loss of its function induces apoptosis in hamster BHK21 cells. By means of a two-hybrid method involving DAD1 as bait, the C-terminal region of Mcl-1, one of the bcl-2 family, was isolated. Consistently, DAD1 binds well to Mcl-1 in COS cells when overexpressed. On deletion analysis, the C-terminal domain of Mcl-1 containing BH(2) (bcl-2 homologous domain) was found to be essential for the interaction with DAD1. On the other hand, the C-terminal half of DAD1 was concluded to be essential for the interaction with Mcl-1. Surprisingly, a DeltaC-DAD1 mutant lacking only 4 amino acid residues from the C-terminus did not complement the tsBN7 mutation, while it interacted well with Mcl-1. In contrast, DeltaN-DAD1 lacking 20 amino acid residues from the N-terminus still exhibited the ability to complement the tsBN7 mutation. Thus, the C-terminus of DAD1 was suggested to play an important role in N-linked glycosylation and to complement the tsBN7 mutation. Mcl-1 may be required for the inhibition of apoptotic cell death caused by a loss of DAD1.

Animals↗
PubMed2000

Mouse T-cell antigen rt6.1 has thiol-dependent NAD glycohydrolase activity.

Mouse Rt6.1 and Rt6.2, homologues of rat T-cell RT6 antigens, catalyze arginine-specific ADP-ribosylation. Without an added ADP-ribose acceptor, Rt6.2 shows NAD glycohydrolase (NADase) activity. However, Rt6.1 has been reported to be primarily an ADP-ribosyltransferase, but not an NADase. In the present study, we obtained evidence that recombinant Rt6.1 catalyzes NAD glycohydrolysis but only in the presence of DTT. The NADase activity of Rt6.1 observed in the presence of DTT was completely inhibited by N-ethylmaleimide (NEM). Native Rt6.1 antigen, immunoprecipitated from BALB/c mouse splenocytes with polyclonal antibodies generated against recombinant RT6.1, also exhibited NADase activity in the presence of DTT. Compared with Rt6.2, Rt6.1 has two extra cysteine residues at positions 80 and 201. When Cys-80 and Cys-201 in Rt6.1 were replaced with the corresponding residues of Rt6.2, serine and phenylalanine, respectively, Rt6.1 catalyzed the NADase reaction even in the absence of DTT. Conversely, replacing Ser-80 and Phe-201 in Rt6.2 with cysteines, as in Rt6.1, converted the thiol-independent Rt6.2 NADase to a thiol-dependent enzyme. Kinetic study of the NADase reaction revealed that the affinity of Rt6.1 for NAD and the rate of catalysis increased in the presence of DTT. Moreover, the NADase activity of Rt6.1 expressed on COS-7 cells was stimulated by culture supernatant from activated mouse macrophages, even in the absence of DTT. From these observations, we conclude that t!he Rt6.1 antigen has thiol-dependent NADase activity, and that Cys-80 and Cys-201 confer thiol sensitivity to Rt6.1 NADase. Our results also suggest that upon the interaction of T-cells expressing Rt6.1 with activated macrophages, the NADase activity of the antigen will be stimulated.

ADP Ribose Transferases↗
PubMed2000

Once-daily theophylline reduces serum eosinophil cationic protein and eosinophil levels in induced sputum of asthmatics.

BACKGROUND: Because eosinophilic airway inflammation is a characteristic feature of bronchial asthma, the treatment of airway inflammation is important in the management of asthma. Theophylline has been reported to reduce airway inflammation, in addition to its well-known bronchodilating effect. OBJECTIVE: In order to evaluate the effects of theophylline on airway inflammation, we investigated 48 subjects with mild and moderate asthma. METHODS: The patients were randomly divided into two groups, with or without theophylline treatment (control n = 24; theophylline, n = 24). We examined the level of serum eosinophil cationic protein (ECP), induced sputum samples, and peak expiratory flow (PEF) and obtained spirograms before and after 4 weeks of treatment with once-daily theophylline (200-600 mg/day) of subjects with mild or moderate asthma. RESULTS: Theophylline significantly increased morning and evening PEF and significantly decreased the diurnal variation of PEF. After treatment with theophylline, both serum ECP and the percentage of eosinophils in induced sputum were significantly decreased. In contrast, peripheral blood eosinophil count was unchanged after treatment with theophylline. CONCLUSIONS: These findings suggest that theophylline reduces airway inflammation and the severity of asthma, presumably via suppression of both eosinophil activity and subsequent eosinophil infiltration of the airways.

Adolescent↗
PubMed2000

Expression of FasL and Fas protein and their soluble form in patients with hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is characterized by a lymphocytic alveolitis and loosely formed granulomas in lung biopsy specimens. HP improves or disappears altogether after cessation of antigen exposure. The Fas-Fas ligand (FasL) system is one of the representative systems of apoptosis-signaling receptor molecules, and is involved in various inflammatory diseases. We hypothesized that the Fas-FasL system may be associated with this disorder. METHODS: We examined the expression of FasL and Fas proteins in lung tissues from patients with HP using immunohistochemistry. We also measured the soluble form of FasL (sFasL) and sFas levels in serum and bronchoalveolar lavage fluid (BALF) from patients with HP using enzyme-linked immunosorbent assay (ELISA). Furthermore, we also measured the cytotoxic activity of BALF sFasL in vitro. RESULTS: FasL was detected in infiltrating mononuclear cells, and Fas was detected in infiltrating mononuclear cells, alveolar macrophages, and epithelioid cells in HP, whereas FasL was not detected and Fas was detected in few alveolar macrophages in controls. The levels of sFasL and sFas in BALF, but not in serum, were significantly increased in HP compared with controls. BALF of HP that included high levels of sFasL had no cytotoxic activity for bronchiolar epithelial cells in vitro. CONCLUSIONS: In HP, there is an upregulation of FasL and Fas in lung tissues. Since there is no incidence of apoptosis and no cytotoxic activity for lung epithelial cells in BALF from patients with HP, the increased levels of BALF sFasL and sFas may reflect the activation and sequestration of inflammatory cells rather than apoptosis.

Alveolitis, Extrinsic Allergic↗
PubMed2000

Prognosis of bronchial artery embolization in the management of hemoptysis.

BACKGROUND: Bronchial artery embolization (BAE) is a well-accepted and widely used treatment modality for the management of massive and recurrent hemoptysis. However, few reports have previously investigated the long-term results. OBJECTIVES: To investigate the prognosis of patients with hemoptysis who had undergone BAE. METHODS: Twenty-two patients with hemoptysis underwent BAE. The underlying diseases included bronchiectasis in 9, aspergillosis in 3, chronic bronchitis in 2, idiopathic bronchial bleeding in 4, and other diseases in 4. The follow-up period ranged from 25 to 88 months (median 47 months). RESULTS: After the initial BAE, 11 of 22 (50%) patients had re-bleeding (5 patients with hemoptysis and 6 patients with minor hemosputa). Among them, 1 patient suffered from recurrent massive hemoptysis and died from airway obstruction within 1 month after BAE. In addition, 10 of these 11 (90.9%) patients experienced recurrent airway bleeding within 3 years after BAE. Recurrent cases of hemoptysis were seen in 6 of 22 patients (27.3%) within 3 years and no case recurred later than 3 years after BAE. A recurrence of hemoptysis was frequently seen in patients with either bronchiectasis or pulmonary-bronchial artery (P-B) shunt. Although BAE is an effective treatment for the immediate control of hemoptysis, 5 of the patients experienced recurrent bleeding in the long-term follow-up. CONCLUSIONS: It is important to follow-up such patients until 3 years after initial BAE, especially when either ectatic changes of the bronchi on a CT scan or a P-B shunt on angiographic findings are detected.

Adult↗
PubMed2000

Histamine-induced increase in isometric tension of smooth muscle is mediated by local vagus nerve in human bronchus.

BACKGROUND: The vagus nerve is reported to play an important role in the regulation of airway responsiveness. OBJECTIVE: In the present study, we investigated the role of the local vagus nerve in the changes in isometric tension of smooth muscle induced by histamine in the human airway. METHODS: Eight human lung tissue specimens were obtained at thoracic surgery, and 24 bronchial smooth muscle strips were used for isometric tension recording. The changes in isometric tension were induced by histamine in the presence or absence of physostigmine (10(-6) M), atropine (10(-6) M), and/or tetrodotoxin (10(-6) M). RESULTS: We found that: (1) histamine induced a dose-dependent increase in the isometric tension in human bronchial smooth muscle; (2) physostigmine (10(-6) M) significantly potentiated the amplitude of the histamine-induced increase in isometric tension; (3) atropine (10(-6) M) significantly suppressed the histamine-induced increase in isometric tension; (4) tetrodotoxin (10(-6) M), did not affect the histamine-induced increase in isometric tension of smooth muscle, and (5) in the presence of tetrodotoxin, atropine significantly suppressed the histamine-induced increase in isometric tension. CONCLUSION: These findings suggest that the histamine-induced increase in isometric tension is mediated partly by acetylcholine, presumably released by the direct action of histamine on the vagus efferent nerve terminals without the central reflex via vagus nerve.

Atropine↗
PubMed2000

Nitric oxide synthase inhibitors attenuate ozone-induced airway inflammation in guinea pigs. Possible role of interleukin-8.

Nitric oxide (NO) is increased in exhaled air of asthmatics. We hypothesized that endogenous NO contributes to airway inflammation and hyperresponsiveness, and that interleukin-8 (IL-8) might be involved in this mechanism. In human transformed bronchial epithelial cells in vitro, NO donors increased IL-8 production dose-dependently. In addition, tumor necrosis factor-alpha (TNF-alpha) plus IL-1beta plus interferon-gamma (IFN-gamma) increased IL-8 in culture supernatant of epithelial cells; the combination of NO synthase (NOS) inhibitors, aminoguanidine (AG) plus N(G)-nitro-L-arginine methyl ester (L-NAME) attenuated the cytokine-induced IL-8 production in epithelial cells. In guinea pigs in vivo, ozone exposure induced airway hyperresponsiveness to acetylcholine and increased neutrophils in bronchoalveolar lavage fluid (BALF), and these changes persisted for at least 5 h. Pretreatment with NOS inhibitors had no effect on airway hyperresponsiveness or neutrophil accumulation immediately after ozone, but significantly inhibited the changes 5 h after ozone. NOS inhibitors also attenuated the increases of nitrite/nitrate levels in BALF and the IL-8 mRNA expression in epithelial cells and in neutrophils in guinea pig airways 5 h after ozone. These results suggest that endogenous NO may play an important role in the persistent airway inflammation and hyperresponsiveness after ozone exposure, presumably partly through the upregulation of IL-8.

Acetylcholine↗
PubMed2000

Effect of eotaxin and platelet-activating factor on airway inflammation and hyperresponsiveness in guinea pigs in vivo.

Although eotaxin causes selective infiltration of eosinophils into the lung, its role in airway hyperresponsiveness remains unclear. We studied the effects of local administration of eotaxin on airway inflammation and hyperresponsiveness in guinea pigs in vivo. Airway responsiveness to inhaled histamine and differential cell counts in bronchoalveolar lavage fluid (BALF) were evaluated 12 h, 24 h, 3 d, and 7 d after intratracheal instillation of eotaxin. Significant eosinophilia in BALF was observed between 6 h and 7 d after eotaxin administration. Histologically, eosinophil accumulation was observed in the airways but not in the alveoli. In contrast, eotaxin did not affect airway responsiveness between 12 h and 7 d after its administration. We then studied the effects on airway responsiveness of subthreshold doses of interleukin 5, leukotriene D(4) (LTD(4)), and platelet-activating factor (PAF) combined with eotaxin. Neither interleukin 5 nor LTD(4) affected airway responsiveness. After eotaxin treatment, PAF significantly enhanced airway responsiveness without further increases in eosinophil counts. Eotaxin plus PAF significantly increased in eosinophil peroxidase activity in BALF compared with control and with eotaxin alone. These data indicate that eotaxin alone causes eosinophil accumulation in the airways but not hyperresponsiveness, and that additional factors such as PAF are needed to activate eosinophils for the development of airway hyperresponsiveness.

Animals↗
PubMed2000

Polycyclic aromatic hydrocarbon carcinogens increase ubiquitination of p21 protein after the stabilization of p53 and the expression of p21.

Polycyclic aromatic hydrocarbon carcinogens (PAHs) and their metabolites have been found to result in a rapid accumulation of p53 gene product in human and mouse cells. However, the induced p53 protein was reported to be transcriptionally inactive. In the present study, the induction of p53 target gene expression after the treatment with either benzo(a)pyrene (B[a]P) or 1-nitropyrene (1-NP) was investigated. A marked induction of messenger RNA (mRNA) expressions of Mdm2, Bax, and p21 was detected in wild-type p53-expressing cells after the treatment with either B[a]P or 1-NP, whereas no significant change in mRNA expression of these genes was observed in p53-negative and mutant cells. 1-NP activated the p21 promoter in a p53-dependent manner. Binding activity of p53 to a p53 consensus sequence increased after the treatment in wild-type p53-expressing cells. Nevertheless, the induced mRNA levels of the p21 did not result in a proportional p21 protein increase, indicating the possibility of post-transcriptional regulation of the protein. With the addition of MG-132, a proteasome inhibitor, to B[a]P or 1-NP treatments, both p21 and p53 protein levels were increased; however, the increase in p21 protein levels was significantly larger than the increase in p53 protein levels. PAHs treatment increased the level of ubiquitinated p21. These results suggest that the p21 product is degraded by the ubiquitin-proteasome system. We conclude that PAHs-induced p53 protein is transcriptionally active.

Benzo(a)pyrene↗
PubMed2000

Soluble form of fas and fas ligand in BAL fluid from patients with pulmonary fibrosis and bronchiolitis obliterans organizing pneumonia.

STUDY OBJECTIVES: The Fas-Fas ligand (FasL) pathway is a representative system of apoptosis-signaling receptor molecules. We previously described that this pathway may play an important role in the pathogenesis of fibrosing lung diseases. In this study, we hypothesized that soluble form of Fas (sFas) and FasL (sFasL) may also be associated with this disorder. MEASUREMENTS AND RESULTS: We measured sFas and sFasL levels in BAL fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF), interstitial pneumonia associated with collagen vascular diseases (CVD-IP), and bronchiolitis obliterans organizing pneumonia (BOOP), using enzyme-linked immunosorbent assay. BALF from all patients was obtained before prednisolone therapy. sFasL levels were relatively increased in IPF patients (p = 0.084), and significantly increased in CVD-IP patients (p < 0.05) and BOOP patients (p < 0.05), compared with control subjects. BALF sFasL levels were elevated in the IPF or CVD-IP subgroups with an indication for prednisolone therapy, compared with those without an indication for therapy. The BALF sFasL level in IPF patients was correlated with the number of total cells and lymphocytes. The BALF sFasL level in BOOP patients was relatively or significantly correlated with the number of total cells or lymphocytes, respectively. The BALF sFas level was significantly increased in BOOP patients, but not in IPF or CVD-IP patients. CONCLUSIONS: We conclude that BALF sFasL levels may be associated with the accumulation of inflammatory cells and reflect the degree of lymphocyte alveolitis in IPF. The elevation of sFasL may be associated with the deterioration of IPF and CVD-IP. The elevation of the BALF sFas level may abrogate the cytotoxicity of FasL in BOOP patients, which may be associated with better prognosis of BOOP, compared with IPF or CVD-IP.

Aged↗
PubMed2000

B7-1, B7-2 and class II MHC molecules in idiopathic pulmonary fibrosis and bronchiolitis obliterans-organizing pneumonia.

Interstitial lung diseases are thought to be associated with the infiltration of activated T-lymphocytes. To induce an effective immune response, antigen-presenting cells have to not only present antigenic peptide with major histocompatibility complex (MHC) molecules to T-lymphocytes but also express B7 molecules. Therefore, the expression of B7-1, B7-2 and class II MHC molecules was investigated in lung tissues from patients with idiopathic pulmonary fibrosis (IPF) and bronchiolitis obliterans-organizing pneumonia (BOOP), and in normal lung parenchyma as a control, using immunohistochemical localization. B7-1 and B7-2 were aberrantly expressed in bronchiolar and alveolar epithelial cells, and class II MHC molecules were also aberrantly expressed in bronchiolar epithelial cells in IPF. B7-1 was aberrantly expressed in bronchiolar epithelial cells in BOOP. There was no significant difference in the expression of these proteins in alveolar macrophages between IPF and control subjects. However, B7-2 and class II MHC molecule expression in alveolar macrophages was decreased in BOOP compared with that in control subjects. Expression of CD28 and CTLA4, receptors for B7 molecules, was detected in infiltrating lymphocytes in lung tissues in IPF and BOOP. It was concluded that bronchiolar and alveolar epithelial cells may actively participate in the pathophysiology of idiopathic pulmonary fibrosis through the aberrant expression of B7 and class II major histocompatibility complex molecules. The dysregulation of these molecules in epithelial cells may lead to the activation of autoreactive T-lymphocytes, which might contribute to the pathogenesis of fibrosing lung diseases.

Adult↗
PubMed2000

[Epidemiology of lung cancer in Japan].

Lung cancer is the most common cause of cancer-related death in both men and women. There are over 51,000 deaths annually from this disease in Japan. The characteristics of lung cancer have changed for several decades. The incidence of the elderly, adenocarcinoma in histology, and stage I disease continues to increase from year to year. In the 1970s, six randomized trials were carried out to evaluate lung cancer screening in the U.S. and Europe. These studies did not contribute to decrease death rate. They concluded there is no evidence to recommend against lung cancer screening. On the other hand, in Japan, several trials by case-control study demonstrated that chest x-ray screening is associated with earlier detection and improved survival. The conclusions are controversial in two studies. Further investigation will be needed to define the benefit of cancer screening.

Age Factors↗
PubMed2000

[Gene therapy for lung cancer treatment].

Gene therapy is a promising strategy for cancer treatment. The strategy is categorized to some fields based on the anti-cancer mechanism. p53 gene therapy and antisense therapy exert the cytotoxic effect on cancer cells by apoptosis induction. In suicide gene therapy, expressed suicide gene product kills the cancer cells in combination with prodrug which metabolite is cytotoxic agent. Oncolytic virus replicates in the tumor selectively and destroys the cancer cells. Immunogene therapy potentiates the antigenicity of cancer cells or activate the immune effector cells. In antiangiogenesis gene therapy, neovascularization is inhibited with antiangiogenic molecule gene such as angiostatin. On the other hand, bone marrow stem cells are protected from high dose anti-cancer agents by the transfer of multi-drug resistant gene.

Cytokines↗
PubMed2000

[Recurrence of catamenial pneumothorax after surgical treatment].

We reported a case of catamenial pneumothorax that was recurrent after surgical treatment. A 43-year-old woman had sudden chest pain and dyspnea during menstruation. Right pneumothorax and pleural effusion were pointed out on chest X-ray films. When the patient was 31 years old, she received a diagnosis of catamenial pneumothorax and underwent thoracotomy for resection of diaphragmatic endometriosis. However, after surgery she experienced recurrence of right pneumothorax, and was accordingly treated with danazol. The patient decided to terminate medication by herself because her symptoms had disappeared. Several years after the cessation of medication, she experienced chest pain frequently during menstruation, but did not seek a medical check-up. She visited our department because of persistent chest pain in 1997. After the patient was hospitalized, pneumothorax was diagnosed and continuous drainage was performed. Although pneumothorax was alleviated by drainage, it recurred during the patient's next menstrual period. Open lung surgery was performed. Diaphragmatic endometriosis with a small hole and inflammatory thickened lesions on the visceral pleura of the lower lobe (S 6) were found and excised. Microscopic examination of the excised specimens showed endometriosis. Visceral pleural endometriosis has been histologically demonstrated in very few cases. After surgery, hormonal therapy was started. The patient has been well for 12 months without recurrence of pneumothorax. Both surgical and hormonal treatment were considered necessary for the treatment of catamenial pneumothorax in this case.

Combined Modality Therapy↗
PubMed2000

[Treatment of lung cancer--state of the art in 2000].

Small-cell lung cancer (SCLC) is, in general, sensitive to anti-cancer chemotherapy and radiotherapy. Standard therapies for extensive SCLC are combination chemotherapies with cyclophosphamide, adriamycin and vincristine (CAV), with cisplatin and etoposide (PE), as well as an alternating CAV/PE program. On the other hand, the standard therapy for limited SCLC is chemoradiotherapy, especially PE and concurrent accelerated hyperfractionated radiotherapy. Based on the therapy, the current state of treatment of small cell lung disease is a median survival time of 10 months and a 3-year survival in 10% of patients with extensive disease, and a median survival time of 30 months and a 3-year survival in 30% of patients with limited disease. Promising trials under investigation including those for dose-intensive chemotherapy, multimodality treatment and combination chemotherapy adopting new drugs are introduced. The standard therapy for inoperable stage III non-small cell lung cancer is a multimodality therapy employing chemotherapy and radiotherapy. However, neither the timing of the radiotherapy nor the optimal combination of anti-cancer agents has yet been established. Nowadays, the combination of cisplatin-based chemotherapy and radiotherapy is expected to bring a median survival time of 15 months and a 3-year survival in 25% of patients. For stage IV non-small cell lung cancer, chemotherapy prolongs survival time by a modest but statistically significant amount of time. For the treatment of inoperable lung cancer, the survival benefit from the use of newly developed drugs with or without platinum is under investigation.

Antineoplastic Combined Chemotherapy Protocols↗