High CC chemokine receptor 7 expression improves postoperative prognosis of lung adenocarcinoma patients.

BACKGROUND: Chemokines and chemokine receptors not only have significant roles in cancer metastasis and tumorigenesis but also act as antitumour agents. The interaction between the Crk-like adaptor protein (CrkL), which is encoded by the CRKL gene, and non-receptor tyrosine kinase c-ABL is reported to transform many cells into malignant cells. We examined the effects of CC chemokine receptor 7 (CCR7), CCR7 ligands and CrkL and c-ABL in lung adenocarcinoma. METHODS: One hundred and twenty patients with lung adenocarcinoma were included in this historical cohort analysis. We examined CCR7 and CCR7 ligands and CrkL and c-ABL mRNA expressions in surgically resected lung adenocarcinoma specimens and evaluated their contribution to prognosis, and the relationship with epidermal growth factor receptor (EGFR) and TP53 mutations. RESULTS: High CCR7 mRNA expressions indicated better prognoses than those of the groups with low CCR7 mRNA expressions (P=0.007, HR=2.00, 95% CI of ratio: 1.22 -3.31). In lung adenocarcinoma, CrkL and c-ABL mRNAs were related to CCR7 mRNA expression (P<0.0001). CrkL and c-ABL mRNA expressions were influenced by EGFR mutations. A high expression of CCL19 was a good prognostic factor of lung adenocarcinoma. CONCLUSION: We propose that CCR7 and CCL19 are clinically good prognostic factors and that CCR7 is strongly related to CrkL and c-ABL kinase mRNA expression in lung adenocarcinoma.

Antitumor cytotoxicity mediated by ligand-activated human V alpha24 NKT cells.

Human V alpha24 NKT cells bearing an invariant V alpha24J alphaQ antigen receptor, the counterpart of the murine V alpha14 NKT cells, are activated by the specific ligand, alpha-galactosylceramide (alpha-GalCer) in a CD1d-dependent manner. Here, we demonstrate that the alpha-GalCer-activated V alpha24 NKT cells exert a potent perforin-dependent cytotoxic activity against a wide variety of human tumor cell lines. In addition, we demonstrate that V alpha24 NKT cells and dendritic cells (DCs) from melanoma patients are functionally normal, even in the tumor-bearing status. The potential use of alpha-GalCer-activated V alpha24 NKT cells and/or DCs from patients for cancer immunotherapy is discussed.

Synthesis and release of deoxycytidine by human B and T lymphoblasts.

Deoxycytidine kinase activity is abundant in human T and B lymphocytes. However, the role of the enzyme in endogenous deoxynucleoside metabolism has not been established. The present experiments show that dividing human B lymphoblasts, but not T lymphoblasts, release substantial amounts of deoxycytidine (dCyd) into the medium, and have an active dCyd-dCMP (deoxycytidine-deoxycytidine 5'-phosphate) substrate cycle. Exogenous dCyd has been shown to protect human lymphocytes from the toxic effects of deoxyadenosine, deoxyguanosine and related compounds. Thus, the differential rates of dCyd release by T and B lymphocytes may affect the sensitivities of the two cell types to the growth inhibitory effects of exogenous deoxynucleosides.

Differential regulation of polyamine synthesis and transmethylation reactions in methylthioadenosine phosphorylase deficient mammalian cells.

The consumption of S-adenosylmethionine during polyamine synthesis and transmethylation reactions yields stoichiometric amounts of 5'-deoxy-5'-methylthioadenosine and S-adenosylhomocysteine, respectively. Information concerning the regulation of the two routes of S-adenosylmethionine metabolism in viable cells under changing growth conditions is limited. The present experiments have measured the time-dependent accumulation of 5'-deoxy-5'-methylthioadenosine and L-homocysteine in the medium of four malignant human and murine cell lines deficient in 5'-deoxy-5'-methylthioadenosine phosphorylase (5'-methylthioadenosine: orthophosphate methylthioribosyltransferase). Included in this group were anchorage-independent and anchorage-dependent cells. The enzyme-deficient cells did not detectably cleave 5'-deoxy-5'-methylthioadenosine, and did not appreciably metabolize homocysteine. A comparison of 5'-deoxy-5'-methylthioadenosine and homocysteine excretion therefore provided a noninvasive method for estimating the relative rates of polyamine synthesis and transmethylation. Early after the release of human CEM lymphoblasts from density dependent growth arrest, 5'-deoxy-5'-methylthioadenosine production increased, and exceeded homocysteine synthesis. 5'-Deoxy-5'-methylthioadenosine formation reached a maximum of 0.9 nmol/12 h per 10(6) cells prior to the onset of exponential growth. The kinetics of homocysteine synthesis were different. Homocysteine accumulation was proportional to the specific growth rate, and achieved a peak of 3.1 nmol/12 h per 10(6) cells during mid-exponential phase, at which time 5'-deoxy-5'-methylthioadenosine production was falling. Similar patterns of 5'-deoxy-5'-methylthioadenosine and homocysteine excretion were observed in other 5'-deoxy-5'-methylthioadenosine phosphorylase deficient cell lines. These data show that polyamine synthesis and transmethylation are differentially regulated during the growth cycle of mammalian cells.

Deoxyadenosine-resistant human T lymphoblasts with elevated 5'-nucleotidase activity.

Although several different enzymes with 5'-nucleotidase activity have been described in mammalian cells, their functions in nucleotide metabolism have not been clearly distinguished. In the present experiments, a mutant human T lymphoblastoid cell line (CEM-dAdoR) was selected specifically for resistance to deoxyadenosine toxicity. Compared to parental CEM cells, the variant had 4-fold elevated ATP-activated cytosolic 5'-nucleotidase activity. Other enzymes of potential importance for deoxyadenosine metabolism were indistinguishable in the two cell types. In medium supplemented with the adenosine deaminase inhibitor deoxycoformycin, the T cells with increased 5'-nucleotidase accumulated less nucleotides from exogenously added deoxyadenosine, or 9-beta-D-arabinofuranosyladenine, than did parental T lymphocytes. These metabolic changes were associated with resistance to the growth inhibitory effects of these nucleosides, and also to deoxyguanosine and to 9-beta-D-arabinofuranosylguanine. The T cells with elevated 5'-nucleotidase activity formed more 2',3'-dideoxyadenosine than did parental cells, in deoxycoformycin-supplemented medium. The accumulation of 2',3'-dideoxyadenosine 5'-triphosphate from 2',3'-dideoxyinosine was similarly augmented in the mutant. These data establish the importance of the cytosolic 5'-nucleotidase for the metabolism of purine 2'-deoxyribonucleosides, arabinonucleosides and 2',3'-dideoxyribonucleosides in T lymphoblasts.

Differential composition of cytosol 5'-nucleotidases between T and B lymphoblasts.

WI-L2 cells (a B-lymphoblastoid cell line) were more resistant than CEM cells (a T-lymphoblastoid cell line) to deoxyadenosine, ara-A (9-beta-D-arabinofuranosyladenine), or ara-C (1-beta-D-arabinofuranosylcytosine) inhibition. This was caused by a difference in the composition of cytosol 5'-nucleotidases between WI-L2 and CEM cells. In intact cells, the endogenous production of deoxyadenosine from WI-L2 cells deficient in adenosine kinase (EC 2.7.1.20) and deoxycytidine kinase (EC 2.7.1.74) was consistently high, despite changes in endogenous adenosine production. Endogenous production of deoxyadenosine from CEM cells deficient in adenosine kinase and deoxycytidine kinase was, however, coordinated with endogenous adenosine production. In broken cells, cytosol dAMPase (2'-deoxyadenosine 5'-monophosphate 5'-nucleotidase) activity of WI-L2 cells was 3-5-fold higher than that of CEM cells. dAMPase activity could be separated from ATP-activated IMPase (inosine 5'-monophosphate 5'-nucleotidase) by gel filtration (molecular weight: dAMPase; 39,000-46,000; ATP-activated IMPase, greater than 150,000). Cytosol ATP-activated IMPase and dAMPase were isolated by phosphocellulose or DEAE-Bio-Gel A chromatography from non-specific phosphatases. The ATP-activated IMPase showed only marginal activity towards dAMP (2'-deoxyadenosine 5'-monophosphate), ara-AMP (9-beta-D-arabinofuranosyladenine 5'-monophosphate), or ara-CMP (cytosine-beta-D-arabinofuranoside 5'-monophosphate), even in the presence of ATP. The activity of ATP-activated IMPase was similar in WI-L2 and CEM cells. dAMPase was separated into two peaks by DEAE-Bio-Gel A chromatography; one of these peaks degraded ara-AMP and ara-CMP. The activities of both peaks from WI-L2 cells were higher than those from CEM cells. These results show that the degradation of dAMP, ara-AMP or ara-CMP was more specific and rapid in WI-L2 than in CEM cells.

Tissue-differential expression of two distinct genes for phosphoribosyl pyrophosphate synthetase and existence of the testis-specific transcript.

Cloning of cDNA coding for rat phosphoribosyl pyrophosphate (PPRibP) synthetase (EC 2.7.6.1) revealed two distinct types of subunit, referred to as PRS I and PRS II (Taira et al. (1987) J. Biol. Chem. 262, 14867-14870). Tissue-specific expression of PRS I and PRS II genes (designated PRPS1 and PRPS2, respectively), was shown for 16 rat organs, using Northern blot analysis. The 2.3 kb PRPS1 mRNA level was high in the brain and adrenal gland, whereas the 3.7 kb PRPS2 mRNA level prevailed in the lung and spleen. Both genes were highly expressed in the thymus, adipose tissue and testis. In other mammals (mouse, calf and human), these two types of mRNA were also detected in various tissues and cell lines. Thus, the expression of each gene is regulated in a tissue-specific manner and there may be functional differences between catalytic and/or regulatory properties of subunits PRS I and II of this enzyme. In the testis, an additional PRPS1-related transcript of 1.4 kb was noted in rats, mice and humans. This transcript may belong to a group of testis-specific gene expressions or functions.

Promoter regions of the human X-linked housekeeping genes PRPS1 and PRPS2 encoding phosphoribosylpyrophosphate synthetase subunit I and II isoforms.

The 5' regions of the human phosphoribosylpyrophosphate synthetase subunit I and II genes (PRPS1 and PRPS2, respectively) were isolated and sequenced. A comparison of the nucleotide sequences between human and rat PRPS1 genes revealed that the sequences around the transcription initiation sites were conserved over 56 nucleotides, and that a TATA-like sequence, a CCAAT box and three putative Sp1 binding sites were present at almost the same positions in the GC-rich sequences. Two major transcription initiation sites were localized in the human PRPS1, one of the two was located 27 nucleotides downstream from the TATA-like sequence, while the upstream initiation site was in the TATA-like sequence. The promoter region of the human PRPS2 gene was also GC-rich and contained a TATA-like sequence, four Sp1 binding sites and a homopyrimidine stretch. The initiation sites were localized at 90 nucleotides upstream from the ATG initiation codon. Chloramphenicol acetyltransferase (CAT)/promoter fusion assays showed that a 2.0 kb region (human PRPS1) and a 1.1 kb region (human PRPS2) possessed the promoter activities in four cell lines. The CAT activities in the three human cell lines tended to correlate with the steady-state mRNA levels of the PRPS1 and PRPS2 genes. These results suggest that the 5' flanking regions cloned contribute to the cell-differential expression of these two genes.

Smoking before surgery predicts poor long-term survival in patients with stage I non-small-cell lung carcinomas.

PURPOSE: The majority of lung carcinoma patients requiring resection have smoking habits prior to surgical treatment, and the correlation of smoking with postoperative complications is well known. However, few studies have investigated the correlation between long-term survival and cigarette smoking in patients with primary, resected lung carcinoma. We analyzed the relationship between clinical factors, including cigarette smoking before surgery, and 10-year survival in stage I non-small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Cigarette smoking habit and other factors influencing either the overall survival or the disease-specific survival rates of patients with stage I primary, resected NSCLC were evaluated according to the Cox proportional hazards model using a total of 369 patients with stage I-NSCLC. RESULTS: Comparison of the cause of death in patients with 30 or more pack-years and patients with less than 30 pack-years showed significant differences in the prevalence of recurrent disease and onset of nonmalignant disease. Multivariate analysis demonstrated significant correlations between overall survival and age and pack-years. Disease-specific survival showed significant correlations with age, tumor classification, and visceral pleural invasion. CONCLUSION: Smoking pack-years is an important clinical prognostic factor in evaluating overall long-term survival in patients with stage I primary, resected NSCLC.

Elevated levels of circulating plasma matrix metalloproteinase 9 in non-small cell lung cancer patients.

Elevated expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 have been implicated as playing important roles in tumor invasion and metastasis in various tissues. We investigated the relationship between circulating plasma MMP-9, its expression in tumor samples, and other clinical features in patients with non-small cell lung cancer (NSCLC). A series of 73 patients (45 men and 28 women) who underwent surgery for NSCLC was used in this study. Preoperative plasma concentrations of MMP-9 were examined using a one-step sandwich enzyme immunoassay. Expression levels of MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were measured in 24 tumor samples by immunohistochemistry. The plasma concentration of MMP-9 in NSCLC patients (71.0 +/- 60.2 ng/ml) was significantly elevated compared to that of healthy volunteers (P < 0.0001). MMP-9 concentrations were elevated in 33 of 73 cases (45.2%), compared with a cutoff value of the mean +/- 2 SD in healthy volunteers. There were statistically significant differences in MMP-9 concentration in adenocarcinoma versus squamous cell carcinoma (P = 0.014) and adenocarcinoma versus large cell carcinoma (P = 0.014). Five of 24 patients (20.8%) had positive immunohistochemical MMP staining of the tumor cell cytoplasm, and two cases had positive staining in the surrounding stromal cells. Plasma MMP-9 concentrations were elevated in 45.2% of NSCLC patients; however, this elevation did not seem to correlate with MMP-9 production by cancer and stromal cells. We concluded that the MMP-9 ELISA could be a beneficial adjunct for assessing the tumor burden of NSCLC, especially for types of squamous cell carcinoma and large cell carcinoma.

Molecular cloning and sequencing of human cDNA for phosphoribosyl pyrophosphate synthetase subunit II.

cDNA clones for human phosphoribosyl pyrophosphate synthetase subunit II (PRS II) were isolated. The five overlapping clones contained 2457 base pairs (bp) covering a 954-bp complete coding region for 318 amino acid residues. Homologies between human and rat PRS II were 99% of the amino acids and 88% of the nucleotides in the coding region. This amino acid homology seems to be the highest so far reported for enzymes involved in nucleotide metabolism and glycolysis. The highly conserved structure may be required for unique catalysis and rigid regulation of this enzyme.

Differential inhibitory effects of auranofin on leukotriene B4 and leukotriene C4 formation by human polymorphonuclear leukocytes.

Auranofin (AF) is a newly introduced oral gold compound having antirheumatic properties, and its efficacy in the treatment of bronchial asthma is now under investigation. In this study, we examined the effects of AF on leukotriene (LT) formation by human polymorphonuclear leukocytes (PMNs) stimulated with the calcium ionophore A23187. AF inhibited LTC4 formation in a dose-dependent manner with an IC50 (concentration required to produce 50% inhibition of control) of 3.2 microM. In contrast, LTB4 formation was not prevented by AF at concentrations up to 6 microM, but it was reduced to 59 +/- 4% (mean +/- SE, N = 3) of control by an 8 microM concentration. As a next step, we explored the mechanisms of the differential inhibitory effects of AF using cell-free systems. When arachidonic acid (AA) and reduced glutathione (GSH) were used as substrates, AF inhibited LTC4 synthesis more effectively (IC50 = 14 microM) than LTB4 synthesis (IC50 = 100 microM). However, LTB4 and LTC4 syntheses from LTA4 were affected only slightly by AF within the concentrations tested (3-100 microM). These results in the cell-free systems indicate that the inhibition of LT formation was caused by a reduction of LTA4 synthesis and that the differential inhibitory effects can be ascribed to the higher Km value of glutathione S-transferase for LTA4 than that of LTA4 hydrolase in PMNs. In accordance with this hypothesis, LTC4 synthesis was more dependent than LTB4 synthesis on LTA4 concentrations within 25-100 microM, and AA-861, a 5-lipoxygenase inhibitor, caused similar differential inhibitory effects on the formation of LTs by intact PMNs. The inhibitory effect of AF on LT formation at physiological concentrations may play some role in the efficacy of this drug.

Prognostic factors in surgical treatment of solitary brain metastasis after resection of non-small-cell lung cancer.

Patients with brain metastasis after resection of non-small-cell lung cancer usually have poor prognosis. A few such patients, however, survive for long periods after surgical resection of brain metastases. To evaluate the prognostic factors in resection of solitary brain metastasis from non-small-cell lung cancer, we reviewed 24 cases undergoing resection of solitary brain metastasis after resection of the primary site from 1977 to 1993. The patient population consisted of 20 men and four women ranging in age from 40 to 75 years old (average, 57.8 years old). None of the patients had systemic metastasis except in the brain at the time of brain surgery. The overall survival rates were 12.5% at 3 years and 8.3% at 5 years after brain surgery. The longest survival periods were 11.5 years after brain surgery and 15.4 years after lung surgery. The interval between lung and brain surgery (< or =360 days vs. >360 days), differentiation of primary cancer (poor vs. moderate), size of primary site (< or =5.0 cm vs. >5.0 cm), and operation of primary site (lobectomy vs. pneumonectomy) significantly affected survival as shown by univariate analysis (P<0.05). Other clinical factors (age, gender, histology, T- and N-status, 'resectability with curative intent' of the primary site, location of the brain metastasis and postoperative radiation therapy) did not affect survival. Multivariate analysis using Cox's proportional hazards model indicated that an interval of more than 360 days between the two surgical procedures (hazard ratio = 0.2351, P = 0.0136) and lobectomy (hazard ratio = 0.5274, P = 0.0416) were independent prognostic factors. In conclusion, patients with solitary brain metastasis from non-small-cell lung cancer without other organ metastasis, in whom relapse in the brain occurred more than 1 year after resection of the primary site and in whom lobectomy was performed, should be treated surgically to maximize the chance of prolonged survival.

Fluorescence bronchoscopy in the detection of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy.

BACKGROUND: A new strategy in the treatment of squamous cell carcinoma of the tracheobronchial tree is the detection and eradication of preinvasive bronchial lesions before they become invasive cancers. It is, however, difficult to detect preinvasive lesions by conventional white-light bronchoscopy alone. PURPOSE: we conducted a detailed investigation on the use of fluorescence bronchoscopy in the detection of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy. METHODS: 64 participants with sputum cytology suspicious or positive for malignancy were examined with both white light and fluorescence bronchoscopy (LIFE group). Earlier to this study, before fluorescence bronchoscopy became available in our institute, 48 participants having sputum cytology suspicious or positive for malignancy were examined with white light bronchoscopy alone (control group). Biopsy specimens for pathological examinations were taken of all abnormal areas discovered by white light or fluorescence bronchoscopy examination. RESULTS: In sputum cytology suspicious or positive for malignancy, the diagnosis of preinvasive bronchial lesions was greatly enhanced in the LIFE group as compared with the control group (45 vs. 7 lesions). The percentage of participants with preinvasive bronchial lesions was also significantly higher in the LIFE group than in the control group (40.6 vs. 12.5%, P = 0.00087, respectively). CONCLUSIONS: Our study suggests that the use of fluorescence bronchoscopy in addition to conventional white-light examination could greatly enhance the detection and localization of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy.

Complete nucleotide sequence of human phosphoribosyl pyrophosphate synthetase subunit I (PRS I) cDNA and a comparison with human and rat PRPS gene families.

cDNA clones for human phosphoribosyl pyrophosphate synthetase subunit I (PRS I) were isolated from a glioblastoma cell line MGC 1 cDNA library. The longest clone contained 2,075 base pairs (bp) almost covering the 2.3-kb mRNA and the base sequence of the coding region (954 bp) had a 92.0% sequence homology with that of rat PRS I cDNA. The deduced amino acid sequences were identical between human and rat PRS I. This perfect conservation has heretofore not been reported for other enzymes involved in nucleotide metabolism and glycolysis. A comparison with other isoforms of this enzyme, PRS II and PRS III, showed that the human PRS I was 79.9 and 92.2% homologous in the coding sequence and 95.3 and 94.0% in the deduced amino acid sequence to human PRS II and PRS III, respectively. The high value of the synonymous difference between PRS I and PRS II cDNAs places their time of divergence long before that of the radiation of mammals. Based on the evolutionary rate of amino acid substitution, the PRS I and II genes probably diverged about 760 million years ago.

Mammalian phosphoribosyl-pyrophosphate synthetase.

PRPP synthetase from rat liver exists as large molecular weight aggregates composed of at least three different components. Cloning of cDNA for the catalytic subunit revealed the presence of two highly homologous isoforms of 34 kDa, designated as PRS I and PRS II. Northern blot analysis showed tissue-differential expression of the two isoform genes. cDNA was expressed in E. coli and studies on the recombinant isoforms showed differences in sensitivity to inhibition by ADP and GDP and to heat inactivation. The rat gene for PRS I has 22 kb and is split into 7 exons. cDNAs for human enzymes were also cloned. Human genes for PRS I and PRS II are localized at different regions on the X-chromosome and their promoter regions were examined. Another component, PRPP synthetase-associated protein of 39 kDa (PAP39), was cloned from cDNA library of the rat liver. The deduced amino acid sequence of PAP39 is remarkably similar to those of PRS I and PRS II. Evidence indicated molecular interaction between PAP39 and the catalytic subunits and an inhibitory effect of PAP39 on the catalytic activity. Expression of the PAP39 gene is tissue-differential like the PRS genes, indicating that the composition of PRPP synthetase may differ with the tissue, hence properties of the enzyme would differ. Further studies on these components and their interaction are expected to reveal various mechanisms governing mammalian PRPP synthetase.

Cytomorphologic features characteristic of tumor stages of thymomas.

The cytologic findings of the tumor cells characteristic of the stages of thymomas were investigated to assess the invasiveness of the tumors. Forty-six patients with thymoma who underwent extensive thymectomy without pre-operative corticosteroid therapy were included in this study. The histologic subtypes included 18 round/oval, 20 mixed, and 8 spindle type. The stages of thymoma classified according to Masaoka's clinicopathological classification included 16 stage I, 20 stage II, 6 stage III, 2 stage IVa, and 2 stage IVb, and myasthenia gravis was recognized in 5 patients. Cytologic findings were retrospectively analyzed in the Papanicolaou-stained stamp smears obtained from the cut surfaces of thymoma specimens. Morphometry of the epithelial tumor cells using Cosmozone-1A was performed to evaluate the validity of our cytologic categories. Compared with the cytologic findings of stage I or II thymomas, those of epithelial tumor cells in stage III or IV more frequently showed necrotic background (50.0%-stage III or IV vs 11.1%-stage I or II, p=0.006), large clusters of epithelial tumor cells (70.0% vs 36.1%, p=0.055), marked nuclear enlargement (90.0% vs 52.7%, p=0.033), marked anisokaryosis (100% vs 52.7%, p=0.006), marked nuclear polymorphism (40.0% vs 5.5%, p=0.004), hyperchromasia (50.0% vs 11.4%, p=0.007) and prominent nucleoli (50.0% vs 16.6%, p=0.028) whereas no significant correlation was observed between cytologic findings and tumor volume. Morphometric studies of thymoma tumor cells revealed that the nuclear size (mean values, 78.8 microm(3)-stage III or IV vs 58.2 microm(3)-stage I or II), the coefficient of variation of the nuclear size (0.326 vs 0.282), and the nuclear rotundity (0.849 vs 0.858) differed significantly between the two categories (p<0.05). Our findings demonstrated that there were significant differences between the cytologic findings of epithelial tumor cells of stage I or II thymomas and those of stage III or IV thymomas, and that the cytologic findings of thymoma tumor cells appear to be useful for distinguishing between non-invasive and invasive thymomas.

Bronchopleural fistula after lung cancer surgery. Multivariate analysis of risk factors.

BACKGROUND: To elucidate retrospectively the risk factors for bronchopleural fistulae after lung cancer surgery. METHODS: The subjects were 1,177 patients with lung cancer who underwent surgery between 1983 and 1997. Twenty-two clinical factors were examined by logistic analysis. RESULTS: Bronchopleural fistulae were observed in 35 patients (32 males, 3 females) with a mean age of 64 years. Eighteen (51%) of 35 patients died of BPF-related complications. The significant risk factors obtained by univariate analysis were male gender, heavy smoking, current smoking, low level of %FVC, metastases to lymph nodes, squamous cell carcinoma, increased WBC, decreased albumin, advanced postsurgical stage, sleeve lobectomy, and resection of the right lower lobe or middle and lower lobe. The significant risk factors noted by multivariate analysis were heavy smoking (30 or more pack/years), current rather than past smoking, metastases to lymph nodes, decreased albumin (3.5 mg/dl or less), and resection of the right lower lobe or middle and lower lobe. CONCLUSIONS: The above risk factors must be taken into account before surgical techniques followed by adequate perioperative management are selected.

Establishment of human monoclonal antibody recognizing a new tumor-associated antigen from a patient with small cell lung carcinoma.

Mouse-human heterohybridoma (3H12) producing human antibody was established by fusing P3/X63-Ag-U1 (P3U1) myeloma cells with lymphocytes from a patient of small cell lung carcinoma (SCLC). This monoclonal antibody reacts to lung cancer cells, especially SCLC, but not to adenocarcinoma or squamous cell carcinoma cells. It does not show any reactivities to other tumors or normal cells so far examined. An immunoprecipitation experiment with this antibody revealed that the antigen on SCLC was a single chain moiety of 150 kilodaltons (Kd). Judging from the cell type reactivity and molecular size of the antigen, this monoclonal antibody appears to detect a new tumor-associated antigen on human SCLC.

[A case of preoperatively diagnosed primary pulmonary leiomyosarcoma].

A 29-year-old woman had been suffering from right back pain for 3 months. Chronic pulmonary thromboembolism was suspected and she was referred to our hospital. She presented with no risk factors for thromboembolism, and during the previous 6 months had lost 4 kg in body weight. Chest radiography showed nodular shadows in the lower field of the right lung. Contrast-enhanced computed tomography demonstrated a filling defect in the right pulmonary artery and nodular lesions in the lower field of the right lung, which were considered to be signs of pulmonary infarction. Absence of perfusion into the right lung was demonstrated by a perfusion scan. Right heart catheterization showed normal pressure in the pulmonary arteries, and pulmonary angiography showed an abrupt cutoff of the right pulmonary artery, which was similar to the finding of pulmonary thromboembolism. A transvenous catheter suction biopsy was performed in the right pulmonary artery and the histopathologic findings yielded a diagnosis of leiomyosarcoma. The patient underwent surgical resection under total cardiopulmonary bypass. A large tumor completely filled the right main pulmonary artery and invaded the posterior wall of the pulmonary trunk close to the left main pulmonary artery. Primary pulmonary leiomyosarcoma is a rare tumor and its prognosis is very poor. Radical surgical resection is the only effective treatment, but early diagnosis is very difficult. Transvenous catheter suction biopsy is a useful procedure for the early diagnosis of pulmonary artery sarcoma.