Tetsuro Kanda

Gene Mutation Analysis and Quantitation of DNA Topoisomerase I in Previously Untreated Non-small Cell Lung Carcinomas

To elucidate whether gene alterations of topoisomerase I (topo I) exist in untreated non‐small cell lung carcinomas (NSCLC), polymerase chain reaction‐single strand conformation polymorphism analysis was performed in forty‐four NSCLC tissue samples. Gene alterations of topo I were sought in three regions, near codons 361 and 363, 533, and 722 and 729, where point mutations have been found in resistant tumor cell lines selected by chronic camptothecin exposure. In addition, nuclear topo I contents were determined by immunoblotting. No mobility shifts were observed compared to the pattern observed in a normal control at any of the three regions in any sample, whereas topo I levels showed an approximately 12‐fold variation. The variation is remarkably large compared to those seen in previous in vitro and in vivo studies. The results suggest that mutations of topo I may not contribute to intrinsic resistance of NSCLC to camptothecins, but low topo I levels may account, at least in part, for the resistance.

Spontaneous remission of a non-small cell lung cancer possibly caused by anti-NY-ESO-1 immunity.

Spontaneous remission of malignant tumors is rare and the biological mechanism of such remission has not been addressed. We report the case of a 71-year-old Japanese patient with non-small cell lung cancer with a right hilar tumor and pleural dissemination that spontaneously regressed. NY-ESO-1 is a cancer/testis antigen that can elicit specific immune responses in patients with cancer. Strong anti-NY-ESO-1 immunity was detected in this patient. His tumor cells expressed NY-ESO-1 and MHC class I molecules. Anti-NY-ESO-1 immunity might have contributed to spontaneous remission in this patient.

Optimal schedule for administering granulocyte colony-stimulating factor in chemotherapy-induced neutropenia in non-small-cell lung cancer

Abstract A prospective randomized study was conducted to determine the optimal schedule of rhG-CSF (recombinant human granulocyte colony-stimulating factor). A group of 33 lung cancer patients treated with MVP therapy (mitomycin, vindesine, and cisplatin) were randomly assigned to three groups: an early prophylaxis group in which rhG-CSF was initiated on day 2 of the MVP cycle; a late prophylaxis group in which rhG-CSF was initiated on day 8; and a therapeutic group in which rhG-CFS was initiated after the onset of neutropenia. Ten patients who had received MVP therapy without rhG-CSF were also analyzed as a no-support group. The incidence of neutropenia was 80% (16/20 courses) in the early prophylaxis group, 44% (8/18) in the late prophylaxis group, 94% (17/18) in the therapeutic group, and 94% (16/17) in the no-support group. The incidence of neutropenia in the late prophylaxis group was less than in the early prophylaxis group (P<0.05), the therapeutic group (P<0.01), and the no-support group (P<0.01). The late prophylactic rhG-CSF schedule was therefore more effective in countering neutropenia than either the early prophylactic or therapeutic schedule.

A case of bronchial aspergillosis caused by Aspergillus udagawae and its mycological features

Aspergillus udagawae and A. fumigatus share similar morphological features but they differ genetically. There is also an important clinical distinction as A. udagawae is less sensitive to amphotericin B than A. fumigatus. We encountered a rare case of bronchial infection due to A. udagawae that was successfully treated with voriconazole. An 82-year-old woman with diabetes mellitus complained of bloody sputum. Bronchoscopy revealed a white plugged region at the origin of the right bronchi B5. Cytological study revealed a clot composed of filamentous fungi and Aspergillus spp. was detected by culture. Molecular analysis revealed that the causative agent was A. udagawae, and voriconazole was used for the treatment. In comparison to A. fumigatus, the A. udagawae strain isolated in this case was less sensitive to amphotericin B, less virulent in immunosuppressed mice, and more sensitive to hydrogen peroxide, features that are almost identical to those of the previously reported isolates of the fungus. We should be aware of the emergence of new Aspergillus species that might pose a clinical threat.

The benefit of cisplatin-based polychemotherapy for adenocarcinoma of the lung

SummaryWe studied the efficacy of cisplatin-based polychemotherapy for adenocarcinoma of the lung. A total of 136 patients were randomized for treatment with either cyclophosphamide, Adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT). Radiation was given to the chests of patients at stage III. The differences in the response rate (35% in the CAPM arm and 13% in the MCT arm) were statistically significant (P <0.01). However, the significant difference was observed in stage-IV patients (CAPM, 33%; MCT, 4%;P <0.001) and not in stage-III patients (CAPM, 40%; MCT, 40%). The median period of survival was 9.5 months for the CAPM arm and 5.5 months for the MCT arm (P <0.035, Wilcoxon-Gehan test;P <0.1, log-rank test). Improved median survival for the CAPM regimen was demonstrated only by stage-IV patients (CAPM, 10 months; MCT, 5.5 months;P <0.025, Wilcoxon-Gehan test;P <0.05, log-rank test). The duration of the response, including PRs and NCs, was significantly different depending on the treatment, showing 5 months for the CAPM arm and 3 months for the MCT arm (P <0.05). The significant difference was also only observed in stage-IV patients. Myelosuppression was more severe with CAPM than with the MCT regimen. Nausea and vomiting were significantly increased in patients receiving the CAPM regimen. However, all toxicities were acceptable and there were no treatment-related deaths. We concluded that cisplatin-based chemotherapy, CAPM therapy, was of more benefit to patients with adenocarcinoma of the lung than MCT therapy.

Application of the COOP/WONCA charts to aged patients with chronic obstructive pulmonary disease: a comparison between Japanese and Chinese populations

BackgroundThe prevalence of chronic obstructive pulmonary disease (COPD) is similar in Japan and China and is increasing due to high rates of smoking in these countries. Reducing COPD is an important public health issue. The goals of this study were to verify the reliability and validity of the Japanese version of the COOP/WONCA charts, a tool for measuring health status, and to examine the qualitative differences in health status between Japanese and Chinese patients with COPD and between these patients and healthy subjects.MethodsFrom 2008 to 2011, we examined the factors affecting the health status of Japanese and Chinese populations living in six cities. Participants were patients with COPD staged according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (140 Japanese, 201 Chinese) and healthy subjects (243 Japanese, 199 Chinese), all 50 to 79 years old. Health status was measured by using the COOP/WONCA charts, and basic information such as smoking status and medical history was reported by the participants.ResultsThe Japanese and Chinese versions of the COOP/WONCA charts were shown to be reliable and valid by test-retest, comparison with the SF-36 and respiratory symptoms, and correlation of results obtained from patients and their physicians. Stepwise multiple regression analyses demonstrated that “Physical fitness”, “Daily activities”, and “Social activities” were predicted by COPD status and/or respiratory symptoms; “Feelings” by nationality and respiratory symptoms; “Pain” by sex and respiratory symptoms; and “Overall health” by nationality. When the COOP/WONCA scores were stratified by nationality, age, sex, and COPD status, the difference of each score between the patients and healthy subjects was larger for the Chinese subjects than for the Japanese. The physical, psychosocial activities, and pain scores increased significantly as COPD status worsened in Chinese subjects, whereas these scores were not affected by sex, age, or COPD status for Japanese subjects. Brinkman index and use of smoky fuel indoors affected the COOP/WONCA scores in Chinese patients but not in Japanese patients.ConclusionsThe Japanese COOP/WONCA charts are reliable and valid. COPD more severely affected the health status of Chinese participants than of Japanese participants. These results suggest that countermeasures against insufficient health care and smoky environments may improve the health status of Chinese patients with COPD.

[A dementia occurred during therapy for multi-drug resistant pulmonary tuberculosis].

A 47-year-old woman was thirdly admitted to our hospital for therapy to multi-drug resistant tuberculosis of the lung in June 88. Although she was treated with TH, PAS and EVM, M. tuberculosis were positive constantly in her sputum. She complained of sleep disturbance, irritability, headache on September 89, she was diagnosed reactive depression. But her symptoms were progressive, low level of intelligence test in November, apatic in December and became spastic paralysis and vegetable state at next year. She was died of pneumonia in November 90. Her autopsy findings showed no brain atrophy nor meningitis. Microscopically, central chromatolysis were showed in Betz cells and anterior horn cells, these findings sometimes suspected for Peragulla, but we could not obtained definite pathological diagnosis, because we could not have been obtained findings indicating for Peragulla. Finally, we reported the clinical course and autopsy findings of dementia occurred during therapy for multi-drug resistant pulmonary tuberculosis.

A case of pseudolymphoma of the lung and submandibular gland.

62才,男性.胸部異常陰影と右顎下腺腫瘤にて入院した. 57才時に,右顎下腺腫瘍摘出術の既往がある.胸部X線像および胸部CTでは,左S4と右S6の浸潤影を認めたものの,肺門および縦隔リンパ節の腫大は認めなかった.また,気管支鏡では右中間気管支幹に小結節が散在してみられた.肺の病変部と顎下腺腫瘍部の病理組織学的所見ではリンパ球の増生がみられ,免疫組織学的にはpolyclonal patternを呈し, pseudolymphomaと診断された. prednisolone, vincristine cyclophosphamideの治療で病変部の改善はみられなかったが, 2年半経過した現在,悪化も認めていない.

A case of primary lung cancer with diffuse sarcoid granuloma in the resected lung.

症例は74才の女性. 7年前よりブドウ膜炎および緑内障にて治療を受け, 胸部X線にて右上肺野に腫瘤影を指摘されていたが放置していたところ, 同陰影が次第に増大の傾向にあるため精査し, 肺腺癌の診断にて右上葉切除を受けた. 切除肺には癌部および非癌部ともにサルコイド肉芽腫をびまん性に認め, 術後の精査にて血清ACE値や, 対側肺の気管支肺胞洗浄液などから, サルコイドーシスの合併が疑われた症例を経験したので報告した.

New β‐Lactamase‐Resistant Cephem Treatment of Guinea Pigs Infected with Legionella pneumophila

The in vivo antimicrobial effect of seven new β‐lactamase‐resistant cephems (cefotaxime, latamoxef, ceftazidime, ceftriaxone, cefotiam, cefbuperazone, and MT‐141) on Legionella pneumophila (strain 81–066, serogroup IV) in guinea pigs was compared with that of erythromycin. As the minimal LD100 within one week was about 4.0 × 109 CFU/ml by intraperitoneal injection of the strain, the animals were inoculated with 2.0 ml of twofold dilutions of a suspension of this bacterium. The animals developed purulent peritonitis and systemic involvement demonstrated by the development of periangitis, pneumonia and pleuritis in the lungs. Three different doses of antibiotics were administered intraperitoneally immediately after the rectal temperature reached more than 40 C. Erythromycin had a significant therapeutic effect but none of the new cephems tested death of the infected guinea pigs.