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Biomedical subjects

S Nawata

Publications and source records attributed to S Nawata.

At least 19 recordsLinked to original sources

[Subjective criteria of chest CT findings for predicting pathological features and postoperative outcomes of small peripheral lung cancer (< or = 2 cm)].

One hundred fifty five patients with completely resected peripheral non-small cell lung cancer, clinically diagnosed 2 cm or less in diameter, are retrospectively reviewed on their preoperative chest CT films, clinico-pathological features, and postoperative outcomes. Pathologic type was classified according to Noguchi's classification. 7% and 8% of all the patients had pathologic N 1 and N 2 diseases, respectively. 19% of all the patients undergone limited resection (segmentectomy or partial resection). Maximum area of the tumor/soft tissue density area of the tumor (M/S ratio) was manually measured by chest CT film. According to the logistic regression analysis, M/S ratio was the only predicting factor of regional lymph node metastasis among factors including pleural indentation, spiculation, and maximum area of the tumor. Univariate analysis showed that maximum area of the tumor, pleural indentation, and M/S ratio were the significant factor for postoperative disease free survival. According to multivariate analysis of postoperative disease free survival with adjustment for operative modality, the result was same as that of univariate analysis. In conclusion, our determined criteria of the chest CT accurately predicted pathological status and postoperative outcome of patients with small peripheral lung cancer. These factors would be useful for stratification factor of prospective clinical study.

Aged↗

Novel forms of squamous cell carcinoma antigen transcripts produced by alternative splicing.

Squamous cell carcinoma antigen (SCCA) is a member of the ovalbumin serine protease inhibitor family, and the serum level of SCCA is a tumor marker of squamous cell carcinoma. Reverse transcription (RT)-PCR of the squamous cell carcinoma cell line showed the existence of a 156 base shorter transcript compared with that of SCCA1 cDNA. By inverse PCR, we cloned the full length cDNA of this SCCA (SCCA1b). Sequence analysis of the complete 1541 bp SCCA1b cDNA showed that it coded for 338 amino acids and had no typical signal sequence in the NH(2) terminus. The cDNA was expressed in Escherichia coli and the product was detected using Western blotting with antibodies against SCCA. Furthermore, RT-PCR of the full coding region of SCCA2 cDNA from cancer tissue showed the existence of a 63 base short transcript (SCCA2b). A comparison of SCCA1b and SCCA2b cDNA with the SCCA1 and SCCA2 genes showed that these messages were derived from each gene by an alternative splicing mechanism.

Alternative Splicing↗

Squamous cell carcinoma antigen suppresses radiation-induced cell death.

Previous study has demonstrated that squamous cell carcinoma antigen (SCCA) 1 attenuates apoptosis induced by TNF alpha, NK cell or anticancer drug. In this study, we have examined the effect of SCCA2, which is highly homologous to SCCA1, but has different target specificity, against radiation-induced apoptosis, together with that of SCCA1. We demonstrated that cell death induced by radiation treatment was remarkably suppressed not only in SCCA1 cDNA-transfected cells, but also in SCCA2 cDNA-transfected cells. In these transfectants, caspase 3 activity and the expression of activated caspase 9 after radiation treatment were suppressed. Furthermore, the expression level of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) was suppressed compared to that of the control cells. The expression level of upstream stimulator of p38 MAPK, phosphorylated MKK3/MKK6, was also suppressed in the radiation-treated cells. Thus, both SCCA1 and SCCA2 may contribute to survival of the squamous cells from radiation-induced apoptosis by regulating p38 MAPK pathway.

Antigens, Neoplasm↗

Suppression of a squamous cell carcinoma (SCC)-related serpin, SCC antigen, inhibits tumor growth with increased intratumor infiltration of natural killer cells.

Squamous cell carcinoma (SCC) antigen (SCCA), a member of the ovalbumin serine proteinase inhibitor family, serves as a circulating marker of squamous cell carcinoma (SC). One of the SCCAs, SCCA1, has been suggested to play a role in the attenuation of apoptosis in vitro and in the augmentation of tumor growth in vivo. In the present study, the infection of a SCC cell line (SKG IIIa) with recombinant retrovirus that expressed the antisense SCCA mRNA suppressed expression of SCCA in vitro. Local administration of this retrovirus into tumors by inoculation in nude mice suppressed tumor growth. Treatment of tumor tissue in vivo is also associated with increased numbers of apoptotic tumor cells and large mononuclear cells in the tumor. To test the possible role of SCCA in the infiltration of large mononuclear cells, we analyzed the effect of SCCA1 on migration of natural killer (NK) cells induced by monocyte-chemoattractant protein-1 in vitro. SCCA1 suppressed migration of NK cells completely, and this inhibitory effect was lost by mutation of the reactive site loop of SCCA1. These results suggest that antisense SCCA may suppress the growth of SCC in vivo not only by the augmentation of intracellular apoptosis but also by the increased infiltration of NK cells into the tumor.

3T3 Cells↗

Nondenaturing two-dimensional electrophoretic analysis of loop-sheet polymerization of serpin, squamous cell carcinoma antigen-2.

Two homologous serine proteinase inhibitors (serpins), squamous cell carcinoma (SCC) antigen-1 and -2 were separated by nondenaturing two-dimensional electrophoresis combined with immunostaining to acquire further information on these proteins under physiological conditions. Polymers of SCC antigen-2 were detected in cytosolic extracts prepared from tumor tissues. The polymer formation of SCC antigen-2 was apparently decreased and the SCC antigen-2-synthetic peptide binary complexes were newly formed by the addition of synthetic peptide with sequences corresponding to residues from P14 to P2 in the reactive center loop of SCC antigen-2. On the other hand, the incubation with synthetic peptides having the sequence of the reactive center loop of SCC antigen-1 or antithrombin had no effect on polymerization of SCC antigen-2. These data suggest that the polymerization of SCC antigen-2 may occur spontaneously in vivo by the loop-sheet mechanism of serpin.

Antigens, Neoplasm↗

Electrophoretic characterization of heat-stable squamous cell carcinoma antigen.

The aim of this study was to investigate the heat stability of squamous cell carcinoma (SCC) antigen, a tumor-associated serine proteinase inhibitor (serpin), in tumor tissue extract by electrophoretic methods. After heat treatment at 70 degrees C for 2 h, the tumor tissue extract showed a single main protein band of 45 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) which reacted with a monoclonal antibody specific for SCC antigen. The heat-stable SCC antigen was separated by two-dimensional electrophoresis (2-DE) into four spots with pI 6.4-5.9 and Mr 44500-45 000 of SCC antigen-1. Furthermore, the SCC antigen-1 still showed its inhibitory activity against a cysteine proteinase, papain, by gelatin zymography. These results suggest that heat treatment of protein sample at 70 degrees C for 2 h may be a useful method for a partial purification of SCC antigen-1 which can inhibit lysosomal cysteine proteinases such as cathepsin L, S, and K.

Antigens, Neoplasm↗

Involvement of reactive oxygen species and nitric oxide in gastric ischemia-reperfusion injury in rats: protective effect of tetrahydrobiopterin.

The purpose of this study was to examine whether tetrahydrobiopterin (BH4), a cofactor of nitric oxide (NO) synthase, attenuates gastric ischemia-reperfusion injury induced by clamping of the celiac artery. Gastric injury was assessed by a formation of gastric mucosal erosions. The gastric injury was observed at 30 and 60 min after reperfusion following 30-min ischemia and was reduced by superoxide dismutase (SOD), catalase, or NO synthase inhibitors. Therefore, reactive oxygen species (ROS) and NO seem to be implicated in the ischemia-reperfusion injury. Treatment with BH4 reduced the ischemia-reperfusion injury. Pretreatment with sepiapterin, a precursor of BH4, also reduced the ischemia-reperfusion injury with an increase in BH4 content in serum and stomach. Both the increase in BH4 content and the protective effect of sepiapterin were prevented of pretreatment with N-acetylserotonin, an inhibitor of BH4 synthesis. These results suggest that the increase in BH4 content may protect against gastric ischemia-reperfusion injury via reduction of ROS and/or NO toxicity. BH4 might be useful as a therapeutic agent for gastric ischemia-reperfusion injury.

Animals↗

Identification of squamous cell carcinoma antigen-2 in tumor tissue by two-dimensional electrophoresis.

The aim of this study was to identify two homologous serine proteinase inhibitor (serpin) molecules, squamous cell carcinoma (SCC) antigen-1 and -2, by two-dimensional electrophoresis (2-DE), combined with immunoblotting, and examine their expression in tumor tissue. The recombinant SCC (rSCC) antigen-1 showed four spots with p/ 6.5, 6.4, 6.3 and 6.0, whereas rSCC antigen-2 showed a more acidic spot with p/5.95. SCC antigen in tumor tissue appeared in three new acidic spots (p/5.7-5.5, M(r) 44 500), numbered 5, 6 and 7, besides the previously reported four spots numbered 1 to 4. These new acidic spots of SCC antigen apparently increased in SCC tissue. Treatment of tissue extract by carboxymethyl (CM)-papain agarose matrix extinguished spots 1 to 4 encoded on the SCCA1 gene, but not 5 to 7 on the SCCA2 gene. Overexpression of the SCCA2 gene may play an important role in the malignant behavior of tumor cells.

Antigens, Neoplasm↗

Cost analysis for thoracoscopy: thoracoscopic wedge resection and lobectomy.

We reviewed our experience with video-assisted thoracic surgery (VATS) in our most recent 80 patients for the purpose of cost analysis. The costs incurred in the patients undergoing a VATS wedge resection for nodules (n = 30) and a VATS lobectomy for lung cancer (n = 10) were compared with the costs in similar patients undergoing a wedge resection (n = 20) and lobectomy (n = 20) using open techniques. The disposable instrument costs were US $1071 higher for a VATS wedge resection; however, the operative time was shorter (0.99 h for VATS versus 1.75 h for the open procedure). The length of hospital stay was also shorter after a VATS wedge resection (10.4 days for VATS versus 16.8 days for the open procedure), thus resulting in lower total hospital charge in the VATS group. The disposable instrument costs were $3190 higher for a VATS lobectomy, and the operative time was longer (5.56 h for VATS versus 4.25 h for the open procedure). The length of hospital stay was similar in both groups (25.2 days for VATS versus 27.7 days for the open procedure), thus resulting in a higher total hospital charge in the VATS lobectomy group. The cost of a VATS wedge resection for removing peripheral nodules is competitive with that of open techniques, but the cost of a VATS lobectomy is higher than that for an open lobectomy.

Costs and Cost Analysis↗

Surgery for abdominal aortic aneurysms associated with malignancy.

Of 148 patients treated for abdominal aortic aneurysms (AAA), 33 (22%) also had cancer. According to the classification of Szilagyi, there were 13 patients in group I, 19 in group II, and 1 in group IV. In group I, the mean interval between the cancer and AAA operations was 7 years (range 1-14 years). Aneurysmectomy was performed in 9 patients, wrapping in 2, and no operation in 2. In group II, a two-stage operation was performed in 8 patients, a single-stage operation in 4, only surgery for cancer in 4, and no operation in 3. Of 4 patients undergoing single-stage operations, 3 had colorectal cancer, and there were no postoperative complications such as graft infection or anastomotic breakdown. In group I, 6 of 13 patients died, but there were no cancer deaths. In group II, 9 of 19 patients died, 6 from progressive cancer. The group IV patient also died of cancer. These results suggest that if a patient can tolerate surgery for both diseases, a single-stage operation is preferable.

Abdominal Neoplasms↗

Biological role of SCC antigen.

SCC antigen is a tumor-associated protein of squamous cell carcinoma of various organs. So far, two genes (SCC Ag-1 and SCC Ag-2) have been identified, and their products are highly homologous and classified as serine protease inhibitors (serpin). Recombinant SCC antigen-1 inhibits chymotrypsin and cathepsin L in vitro, indicating that it is inhibitory type serpin. Transduction of tumor cells with SCC antigen-1 reveals that SCC antigen-1 inhibits apoptosis of tumor cells induced by anticancer drug, TNFalpha or NK cells. Therefore SCC antigen-1 may work in cancer cells for tumor growth, and in normal squamous epithelium for differentiation by means of the inhibition of apoptosis. Recombinant SCC antigen-2 inhibits cathepsin G and mast cell chymase, suggesting that it protects epithelial cells from the inflammation induced by these proteases.

Antigens, Neoplasm↗

Dissecting aortic aneurysm involving an anomalous right subclavian artery and isolated left vertebral artery: case report and review of the literature.

A 54-year-old hypertensive woman was admitted with severe interscapular back pain. A chest radiograph showed marked widening of the mediastinum. Aortography demonstrated a DeBakey type III, a thoracic aortic dissection and an anomalous right subclavian artery which was associated with an isolated left vertebral artery. The patient underwent aortic arch replacement with 5 branches and made an uneventful recovery. As far as we can determine, this is the first reported occurrence of these anomalies together with acquired disease of the aorta.

Aortic Dissection↗

Electrophoretic analysis of the "cross-class" interaction between novel inhibitory serpin, squamous cell carcinoma antigen-1 and cysteine proteinases.

We investigated the "cross-class" interaction between cysteine proteinases and a novel inhibitory serpin, recombinant squamous cell carcinoma (rSCC) antigen-1, which inhibits a serine proteinase, chymotrypsin. rSCC antigen-1 inhibited the cysteine proteinases, papain, papaya proteinase IV and cathepsin L. Interestingly, although rSCC antigen-1 formed sodium dodecyl sulfate (SDS)- and heat-stable complexes with chymotrypsin, rSCC antigen-1 gave the 40 kDa fragment and small molecular mass peptide by incubation with papain without forming an SDS- and heat-stable complex. The cleavage was observed between the Gly353-Ser354 bond, indicating that rSCC antigen-1 interacts with cysteine proteinases not at the predicted reactive site P1-P1' portion (Ser354-Ser355), but at the Gly353-Ser354 of the P2-P1 portion. These findings promote understanding of the "suicide inhibition" mechanism of SCC antigen-1 against cysteine proteinases.

Animals↗

Adenoviral thymidine kinase prodrug gene therapy inhibits sarcoma growth in vivo.

Local recurrence of sarcoma is due to residual tumor cells remaining after surgical resection and is associated with decreased survival. We implemented adenoviral-mediated transfer of the herpes simplex thymidine kinase (HSTK) gene with subsequent ganciclovir (GCV) administration to treat a model of residual sarcoma, [3H]Thymidine uptake in MCA sarcoma cells was determined after infection with replication incompetent adenovirus of the AdMLP.HSTK construct in the presence of GCV. In vivo efficacy was evaluated in a model of residual sarcoma when 9 mg of MCA tumor was implanted into the latissimus muscle of Fischer 344 rats. Three days after implantation, animals were randomized to receive AdMLP.HSTK, AdCMV. Null, or viral suspension buffer intratumorally. From Day 4, animals were administered b.i.d. GCV (50 mg/kg) or saline ip. Tumors were excised on Day 14 and weighed. Statistical analysis was by Mann-Whitney U test. In vitro: [3H]thymidine incorporation was significantly decreased in MCA sarcoma cells infected with AdMLP.HSTK in the presence of GCV (P < 0.05). In vivo: Growth of MCA sarcoma treated with AdMLP.HSTK and GCV was significantly inhibited. Final tumor weights in the AdMLP.HSTK/GCV group were lower than all control groups (P < 0.05). A significant antitumor growth effect on MCA sarcoma was seen with adenoviral-mediated transfer of the HSTK gene and GCV administration, both in vitro and in an in vivo model of residual disease. This prodrug gene therapy strategy warrants investigation as an adjuvant modality in the management of sarcoma.

Adenoviridae↗

Combined thoracoscopic lung resection and laser ablation for lung cancer with pulmonary emphysema: report of a case.

We report herein the case of the 71-year-old man with lung cancer and pulmonary emphysema requiring supplementary oxygen at 21/min by nasal cannula for whom thoracoscopic wedge resection of an adenocarcinoma in his left lower lobe was successfully performed. During the same procedure, thoracoscopic laser ablation of pulmonary bullae was also carried out. There were no postoperative complications, and the patient is currently well 12 months following surgery without any evidence of local or regional recurrence, or distant metastasis. His severe dyspnea on exertion improved, and he no longer requires supplementary oxygen.

Adenocarcinoma↗

Chest wall implantation of lung cancer at the drainage tube site: report of a case.

We report herein the case of a 70-year-old man in whom a chest wall implantation of adenocarcinoma of the lung at the drainage tube site was found 4 months after a right lower lobectomy with mediastinal lymph node dissection had been performed for adenocarcinoma of the right lower lobe. The lesion was successfully treated by tumor extirpation. We believe that tumor seeding to the chest wall occurred at the time of thoracotomy. To prevent such tumor seeding, the pleural cavity should be washed out routinely with a massive volume of physiological saline solution prior to closure of the chest wall.

Adenocarcinoma↗

Sequential bilateral isolated lung perfusion in the rat: an experimental model.

BACKGROUND: A model of isolated single-lung perfusion in the rat has been established in our laboratory to study the chemotherapeutic treatment of pulmonary metastases. A sequential bilateral isolated lung perfusion model was designed to investigate the feasibility of staged perfusions in the rat. METHODS: Twenty-four Fischer rats were randomized into three experimental groups of 8 rats each. All rats underwent left isolated lung perfusion. One, 2, or 3 weeks later, the rats in groups I, II, and III, respectively, underwent contralateral (right) perfusion. Five control animals (group IV) underwent sequential bilateral sham thoracotomies 1 week apart. Arterial blood gas analysis was performed 1 week after the second operation in the rats in groups I and IV. RESULTS: All animals survived the first operation, with 100% (8/8), 75% (6/8), and 100% (8/8) of the animals in perfusion groups I, II, and III, respectively, surviving the second operation. All control animals (group IV) survived the second sham thoracotomy. Arterial blood gas analysis did not show a significant difference in the oxygen or carbon dioxide partial pressure or the pH between group I and IV (p = 0.32, 0.96, and 0.76, respectively). CONCLUSIONS: Our experiments demonstrate that sequential bilateral isolated lung perfusion is safe in and well tolerated by the rat. This model can be used to investigate the safety and efficacy of staged perfusions with chemotherapeutic agents in the treatment of bilateral pulmonary metastases in the rat.

Animals↗

Isolated lung perfusion with doxorubicin prolongs survival in a rodent model of pulmonary metastases.

BACKGROUND: We developed a rodent model of unilateral pulmonary metastases to evaluate long-term survival after isolated lung perfusion with doxorubicin. METHODS: In the model development study, on day 0, two groups of F344 rats (n = 15) underwent transient right pulmonary artery occlusion for either 5 or 10 minutes at the time of intravenous injection of methylcholantrene-induced sarcoma cells. On day 14, all animals were sacrificed and lung nodules counted. In the survival study, on day 0, 21 rats received intravenous injection of sarcoma cells with concomitant 10-minute right pulmonary artery occlusion. On day 7, eight rats underwent left isolated lung perfusion with doxorubicin (6.4 mg/kg); five rats underwent perfusion with buffered Hespan; six untreated rats were studied as controls. RESULTS: Ten of fifteen animals (67%) in the model study with 5-minute pulmonary artery occlusion had right-sided tumor nodules. Ten-minute occlusion resulted in a tumor-free right lung in all animals. In the survival study, all animals in the Hespan and control groups died of massive tumor replacement of the left lung, with median survival times of 20 and 18 days, respectively. The median survival time of 36 days for the animals undergoing isolated lung perfusion with doxorubicin was significantly longer (p < 0.00001). The left lung of two of the doxorubicin perfused rats was tumor-free at 6 weeks. CONCLUSIONS: Isolated lung perfusion with doxorubicin results in a durable response and prolongs survival in the treatment of experimental sarcoma pulmonary metastases.

Animals↗