千代 雅子

DNA polymerase theta (Pol theta) is a recently identified family A polymerase that contains an intrinsic helicase domain. Drosophila Pol theta mutants are hypersensitive to bifunctional DNA crosslinking agents and exhibit an elevated frequency of spontaneous chromosomal aberrations, suggesting a role for Pol theta in repair of DNA interstrand crosslinks and in the general maintenance of genome stability. To investigate a possible involvement of Pol theta in tumorigenesis, we have examined its expression in various normal and malignant tissues. Paired tumor and adjacent nontumorous tissues from patients with lung (n = 27), stomach (n = 28) and colon (n = 26) cancer, as well as 26 normal human tissues, were examined for Pol theta expression by RT-PCR, Northern or Western blot analysis. Pol theta was predominantly expressed in primary lymphoid organs including the fetal liver, thymus and bone marrow where lymphocyte progenitors undergo V(D)J rearrangements of their antigen receptor genes. In addition, Pol theta expression was upregulated in germinal center B cells, in which class switch recombination of the immunoglobulin genes occurs. Examination of Pol theta expression in matched cancer specimens revealed that Pol theta was barely detectable in the nontumorous tissues but was upregulated in 17 of 27 (63%) lung, 11 of 28 (39%) stomach and 20 of 26 (77%) colon cancers. Moreover, patients with high levels of Pol theta expression had a significantly poorer clinical outcome compared with those expressing low levels of Pol theta. These results implicate that Pol theta may have a specialized function in lymphocytes and that its overexpression may contribute to tumor progression.

The radial endobronchial ultrasound (EBUS) probe is conventionally inserted through the working channel of the flexible bronchoscope and limits interventional diagnostics and therapeutics under direct ultrasound control. The aim of this study was to assess the new convex probe EBUS (CP-EBUS) in the visualization of the hilar lymph nodes in surgically resected specimens and explore its feasibility to perform transbronchial needle aspiration (TBNA) under direct EBUS guidance prior to its clinical use. Fourteen surgically resected specimens from lung cancer (n=12) and metastatic lung cancer (n=2) patients were included in the study. The resected specimens included eight right upper lobes, one right middle lobe, and five left lower lobes. The EBUS examination was performed with a flexible bronchoscope equipped with a 7.5 MHz convex probe (CP) that scans parallel to the insertion direction of the bronchoscope. The appearance of the hilar lymph nodes using this CP-EBUS was noted. The size of hilar lymph nodes was measured at CP-EBUS and compared with the actual size of the lymph nodes, which was measured with a Vernier's caliper. Hilar lymph nodes could be clearly visualized with CP-EBUS. There was a good correlation between the actual size of the lymph node and that measured using CP-EBUS (R(2)=0.950). A dedicated transbronchial aspiration needle could be inserted into the hilar lymph node under direct ultrasonic control. There is a possibility in the underestimation of the size of large lymph nodes due to the scanning nature of the convex probe. The CP-EBUS was successfully used to visualize the hilar lymph node and perform TBNA in surgical resected lung specimens. This technique has an excellent potential to perform direct ultrasound guided TBNA of mediastinal and hilar lymph nodes.

Interleukin (IL)-23 and IL-27 have been recently identified as members of the IL-12 heterodimeric cytokine family. The cytokines are released from activated dentritic cells and play a crucial role in cell-mediated immunity. Expression profiles of the cytokines' receptors suggest that target cells of the cytokines are distinct depending on T cell maturation and differentiation. We first examined whether murine colon carcinoma cells (Colon 26) expressing IL-27 (Colon 26/IL-27) could produce antitumor effects in syngeneic mice. The mice developed small Colon 26/IL-27 tumors and subsequently rejected them, whereas parent tumors continued to grow. Since Colon 26/IL-12 and Colon 26/IL-23 cells were also rejected in syngeneic mice, we then investigated the combinatory antitumor effects of the cytokines. We inoculated Colon 26/IL-12, Colon 26/IL-23, Colon 26/IL-27 cells or mixed populations of the cytokine producers into one flank of the mice that simultaneously received parent tumors in the other flank. The parent tumor growth influenced by the cytokine producers was similar to each other. Combinatory antitumor effects were not produced by the cytokine producers and application of the cytokines did not show any synergistic effects.

Background: We investigated the use of high magnification bronchovideoscopy combined with narrow band imaging (NBI) for the detailed examination of angiogenic squamous dysplasia (ASD). This was carried out in relation to bronchial vascular patterns with abnormal mucosal fluorescence in heavy smokers at high risk for lung cancer. Methods: Forty eight patients with sputum cytology specimens suspicious or positive for malignancy were entered into the study. Conventional white light and fluorescence bronchoscopic examination was first performed. Observations by high magnification bronchovideoscopy with conventional white light were made primarily at sites of abnormal fluorescence, and then repeated with NBI light to examine microvascular networks in the bronchial mucosa. Spectral features on the RGB (Red/Green/Blue) sequential videoscope system were changed from the conventional RGB broadband filter to the new NBI filter. The wavelength ranges of the new NBI filter were B1: 400 - 430 nm, B2: 420 - 470 nm, and G: 560 590 nm. ASD tissues were also examined using a confocal laser scanning microscope equipped with argon-krypton (488 nm) and argon (514 nm) laser sources. Results: The microvessels, vascular networks of various grades, and dotted vessels in ASD tissues were clearly observed in NBI-B1 images. Diameters of the dotted vessels visible on NBI-B1 images agreed with the diameters of ASD capillary blood vessels diagnosed by pathological examination. Capillary blood vessels were also clearly visualised by green fluorescence by confocal laser scanning microscopy. There was a significant association between the frequency of dotted vessels by NBI-B1 imaging and tissues confirmed as ASD pathologically ( p = 0.002). Conclusions: High magnification bronchovideoscopy combined with NBI was useful in the detection of capillary blood vessels in ASD lesions at sites of abnormal fluorescence. This may enable the discrimination between ASD and another pre-invasive bronchial lesion.

BACKGROUND: This study investigated postoperative morbidity, mortality, and the long-term survival for patients with lung cancer who have interstitial lung diseases. METHODS: A retrospective chart review of 931 patients with lung cancer who underwent pulmonary resection at Chiba University Hospital between 1990 and 2000 was undertaken. Interstitial lung disease was defined by medical history, physical examination, and abnormalities compatible with bilateral lung fibrosis on chest computed tomography or high-resolution computed tomography (36 patients: 3.9%, interstitial lung diseases group). The remaining 895 patients (96.1%) were categorized as non-interstitial lung disease group. RESULTS: The incidence of postoperative pneumonia and acute or exacerbation of interstitial pneumonia was higher in the interstitial lung disease group (all P <.05). Thirty-day mortality was statistically equivalent between the interstitial lung disease and the non-interstitial lung disease groups (P =.30). The 5-year overall survivals were 62.5% (non-interstitial lung disease) and 35.6% (interstitial lung disease). Respiratory failure was the second main cause of death after the recurrence of primary cancer in the interstitial lung disease group. The risk factors for long-term mortality were interstitial lung diseases, advanced pathologic stage, male sex, high age, and positive smoking history (all P <.05). CONCLUSIONS: Interstitial lung disease was a risk factor for developing postoperative morbidity and mortality and poor long-term survival due to the occurrence of respiratory failure.

BACKGROUND: The aim of this study was to evaluate the influence of chronic obstructive pulmonary diseases (COPD) on postoperative pulmonary function and to elucidate the factors for decreasing the reduction of pulmonary function after lobectomy. METHODS: We conducted a retrospective chart review of 521 patients who had undergone lobectomy for lung cancer at Chiba University Hospital between 1990 and 2000. Forty-eight patients were categorized as COPD, defined as percentage of predicted forced expiratory volume at 1 second (FEV1) less than or equal to 70% and percentage of FEV1 to forced vital capacity less than or equal to 70%. The remaining 473 patients were categorized as non-COPD. RESULTS: Although all preoperative pulmonary function test data and arterial oxygen tension were significantly lower in the COPD group, postoperative arterial oxygen tension and FEV1 were equivalent between the two groups, and the ratio of actual postoperative to predicted postoperative FEV1 was significantly better in the COPD group (p < 0.001). With multivariable analysis, COPD and pulmonary resection of the lower portion of the lung (lower or middle-lower lobectomies) were identified as independent factors for the minimal deterioration of FEV1. Actual postoperative FEV1 was 15% lower and higher than predicted, respectively, in the non-COPD patients with upper portion lobectomy and the COPD patients with lower portion lobectomy. Finally, we created a new equation for predicting postoperative FEV1, and it produced a higher coefficient of determination (R(2)) than the conventional one. CONCLUSIONS: The postoperative ventilatory function in patients with COPD who had lower or middle-lower lobectomies was better preserved than predicted.

We investigated the XBF-4B40 (4B40) thin bronchoscope, which has a 4.0-mm outer diameter and a 2.0-mm biopsy channel, and studied its impact on the diagnosis of lung carcinoma. We analyzed 30 peripheral lung carcinoma cases by performing bronchoscopic examination using the 4B40 and the type 200 videoscope and recorded the most distal bronchus level reached. In addition, transbronchial aspiration biopsy, forceps biopsy, or brushing was performed, and the diagnosis accuracy between the two instruments was determined. The mean of the most distal bronchus reached by the 4B40 and the type 200 videoscope was the 4.5th and the 3rd, respectively. The 4B40 reached significantly further into the distal bronchus than the type 200 videoscope (p<0.0001). Accuracy for lesions detected in the right segment 1 or left segment 1+2 using the 4B40 and the type 200 videoscope was significantly different (p<0.0001) at 90.0 and 0%, respectively. The new type of bronchoscope, XBF-4B40, is useful for peripheral pulmonary lesion diagnosis with diagnosis accuracy improvements in the right segment 1 or the left segment 1+2.

We report a surgical case involving localized honeycomb lung with mucus, caused by colonization of a Schizophyllum commune, which displayed a tumorous shadow in the right upper mediastinum. A 74-year-old male with a history of tuberculosis in the 1970s was referred to Chiba University Hospital (Chiba, Japan) with an abnormal shadow evident in the chest roentgenogram. A transbronchial biopsy failed to yield a definite diagnosis. We resected the right upper lobe, which was found to contain a consolidative lesion filled with viscous mucus in the right upper lobe adjacent to the right upper mediastinum. Microscopic examination revealed a honeycomb lung formation with mucus in the destroyed space. Culture of the mucus yielded a whitish filamentous fungus, positively identified as S. commune. This is the first report of S. commune leading to a deposit of mucus and the formation of a consolidative lesion in the destroyed lung.

Primary liposarcomas of the mediastinum are very rare. We report on a 13-year-old girl who presented with a huge mediastinal tumor. The tumor was extirpated by a median sternotomy with a right thoracotomy. The tumor included the superior vena cava in the anterior mediastinum. It therefore probably originated from the anterior mediastinal fat tissue, possibly from the thymus. A pathological examination revealed myxoid liposarcoma. At 35 months postoperatively, the patient has not shown any recurrence.